Thao K. Adams, PharmD, BCOP

The gold standard for localized nonmelanoma skin cancer (NMSC) treatment in the vast majority of patients is surgery and radiation therapy (RT), but treatment of advanced or metastatic NMSC may require systemic methods given the poor prognosis.

 New and emerging treatment modalities for advanced NMSC provide hope for this patient subset. 

“I think the biggest thing that’s happened in the field and one of the reasons I’m enthusiastic about it is that there have been tremendous changes… very recently for both cutaneous squamous cell carcinoma and basal cell carcinoma,” said Michael K. Wong, MD, PhD, FRCPC, a professor in the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center, during an interview with 

Although cemiplimab (Libtayo) and pembrolizumab (Keytruda) have received FDA approval for use in cutaneous squamous cell carcinoma (CSCC), realworld data on tolerability and effi cacy are scarce, which has led to investigatory studies.

The real-world clinical outcome and tolerability of cemiplimab-rwlc was evaluated in a retrospective cohort trial in the Netherlands.

 Objective clinical response was achieved in 50% of patients, with 13.6% having a complete response (CR; n = 66). The median progression-free survival (PFS) and overall survival (OS) rates were not reached after a median follow-up of 11.7 months. The most common adverse events (AEs) were fatigue and pruritis in 48.5% and 30.3% of patients, respectively. Real-world analysis of cemiplimab use demonstrated similar response rates to those of clinical trials and the drug was tolerable for patients with CSCC.

Another trial that evaluated the real-world pattern of treatment in CSCC was performed in the United States using retrospective, observational data captured from health care claims from commercial health coverage or private Medicare supplemental coverage.

 Results demonstrated that between 2013 and 2019, 75.8% of patients received chemotherapy, 51.7% of patients received RT, and 35.7% of patients received targeted therapy as fi rstline treatment (n = 207). Cetuximab was the most common targeted therapy in the fi rst-line setting. However, the investigators concluded that results may not be refl ective of emerging real-world treatment patterns in the most recent years. They performed an analysis of the mortality using the National Death Index in 126 patients and found an OS of 76% at 6 months and 50% at 12 months post index date. Median survival without surgery or RT 180 days post index date was 11.2 months. Additionally, health care–related expenditures were mainly attributed to outpatient costs.

Checkpoint inhibitors have been at the forefront of systemic therapy in advanced CSCC with the FDA approval of cemiplimab and pembrolizumab (Keytruda) in this patient population. 

Wong said, “The 2 approved agents, cemiplimab and pembrolizumab, have propelled the field forward by showing significant objective response rate [ORR (achieved in approximately half of patients)] and a CR [rate around the 10% to 15% range. The results are] something very unusual considering that all we had before in the systemic space was combination cytotoxic chemotherapy or anti-EGFR drugs that are given as monotherapy or in combination with RT.” 

The FDA’s granting an expanded label indication for pembrolizumab for the treatment of advanced CSCC was based on data from KEYNOTE-629 (NCT03284424), a multicenter, multicohort, nonrandomized, open-label trial. The ORR was 50% (n = 54). The AE profile was similar in CSCC compared with other malignancies.5 Cemiplimab and pembrolizumab have been incorporated into the standard of care as firstline treatment for advanced CSCC; however, the question of therapy sequencing remains unanswered. A study evaluated the sequential use of cemiplimab following progression on immunotherapy.

 Eleven patients were in cohort A, consisting of patients who received cemiplimab after immunotherapy, and 2 patients were in cohort B, consisting of those who received cemiplimab not immediately following immunotherapy. The ORR was 54% in cohort A and the cumulative 6-month disease control rate (DCR) was 77%. In cohort B, both patients had progressive disease (PD) as best response. Common AEs with cemiplimab included rash and hypomagnesemia. Investigators noted a high and durable response rate in cohort A, which requires validation in a larger patient population.

On the sequencing of immunotherapy, Wong said, “The idea of sequencing with all current strategies [is an] extremely important question. There’s no answer to that yet. Certainly we’re learning from other cancers that are using immunotherapy, notably melanoma. All those questions that we’ve asked in melanoma, we’re now asking in squamous cell carcinoma and basal cell carcinoma as well.” Another potential emerging treatment option for patients with CSCC is nivolumab (Opdivo) in the first-line setting.

 A single arm phase 2 trial in treatment-naïve patients with advanced CSCC demonstrated an ORR at 24 weeks of 58.3% (n = 24). The median PFS was 12.7 months and estimated OS was 20.7 months. RT prior to nivolumab was associated with worse outcomes (P = .035). Overall, AEs were tolerable, and those related to nivolumab occurred in 87.3% of patients with the majority being grade 1 or 2. The investigators concluded that the findings from this trial further affirm checkpoint inhibitors as the standard of care in advanced CSCC.

Historically, patients with basal cell carcinoma (BCC) have had limited treatment options. “We’ve really had to resort to the toolbox that we had which was surgery, radiation. Perhaps the first breakthrough we had was in basal cell carcinoma where there was this recognition of a molecular pathway called a hedgehog pathway....” Wong said. “We recognize that there was a large proportion of these basal cell cancers which had aberrations in the hedgehog pathway resulting in the turning on of this pathway as a prerequisite for the cancer. By definition, inhibition of the same pathway would result in tumor regression…. For almost a decade now we’ve had the use of hedgehog inhibitors (HHIs) for basal cell carcinoma with more than half of the patients [responding to therapy], and if you add disease control rate, it’s even higher,” he continued. 

A retrospective cohort study evaluated the characteristics and outcomes of patients who discontinued first-line treatment of HHIs in advanced BCC.

 A total of 73 patients discontinued first-line treatment with HHIs; 4 patients were included in the second-line initiators group and 15 were in the second-line noninitiators group. Fourteen patients discontinued fi rst-line HHI therapy because of toxicity and those patients were in the second-line noninitiators group. An additional 4 patients discontinued first-line HHIs because of disease progression and were in the second-line initiators group. One patient who discontinued first-line HHIs because of disease progression was in the second-line noninitiators group. The median time at which HHIs were discontinued was 9 months in the second-line initiators group and 7 months in the second-line noninitiators group. The time to fi rst-line HHI discontinuation was consistent with that of previous studies. The investigators found an unmet need for effective second-line treatment for patients after first-line HHI discontinuation in advanced BCC.

Clinical trials have attempted to bridge the unmet gap of standard of care for second-line treatment of advanced BCC. In the past year, the FDA granted regular approval for cemiplimab for patients with locally advanced or metastatic BCC after treatment with HHIs or those who are unable to receive an HHI based on results from Study 1620 (NCT03132636), an open-label, multicenter, nonrandomized trial. In patients with locally advanced BCC, the ORR was 29% (n = 84). Additionally, in metastatic BCC, the ORR was 21% (n = 28).

Wong said, “Now we have a new possibility in the use of anti–PD-1 immunotherapies, specifi cally cemiplimab. What has happened at ESMO [European Society for Medical Oncology] and ASCO [American Society of Clinical Oncology] are a slew of [results from] studies showing response rates in specifi c subsets or patients in community practice all in line with what we know is happening, which is [that cemiplimab] is an active therapy and gives us opportunities in the [HHI]-refractory space, which is something that we’ve not had before. Cemiplimab has filled an [unmet gap] in a significant way because one of the things is that patients achieve complete responses… and that’s a big deal.” 

In addition to systemic targeted therapies in BCC, topical therapy with remetinostat, a histone deacetylase (HDAC) inhibitor, has also shown efficacy and safety for local treatment of BCC as an alternative to surgery.

 In the study, 27 patients with 45 tumors were included in the intentionto-treat analysis (FIGURE10). 

According to Wong, “There’s been a tremendous amount of effort using immunomodulatory agents [in different drug delivery methods and]…we have tried to address this unmet gap in our therapeutic armamentarium. The use of topical HDAC inhibitors is along the same vein, but we don’t have good data yet to establish these as standards of care. Nevertheless, these are attempts to elucidate an immune response in an organ that has suffered prolonged and excessive UV radiation damage.” 

One of the newer therapies approved for Merkel cell carcinoma (MCC), a rare and aggressive subset of skin cancer, is avelumab (Bavencio), an anti–PD-L1 immune checkpoint inhibitor. Results from the JAVELIN Merkel 200 trial (NCT02155647) led to the FDA approval of avelumab in MCC.

Sandra D’Angelo, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, said, “The JAVELIN Merkel 200 study was conducted in 2 parts. The first part was a second-line postchemotherapy clinical trial [in which] a number of patients with MCC received avelumab at the time of progression on chemotherapy. [The results] formed the initial basis that led to the FDA approval of avelumab for MCC. In addition, the second part of the study was in a treatment-naïve cohort [who received] avelumab.”

Long-term data were presented at ASCO regarding patients who received at least 1 line of therapy prior to avelumab.

 The results demonstrated clinically meaningful OS of 12.6 months after 65.1 months of median follow-up in 88 patients. The OS rate at 48 months was 30% and at 60 months was 26%. The treatment discontinuation rate was 12.5%, with the most common reason for discontinuation being disease progression followed by AEs. Most patients, 71.6%, had died at the time of data cutoff, none as a result of avelumab-related AEs. Long-term results from this study solidify avelumab as the standard of care in patients with metastatic MCC after progression on at least 1 line of chemotherapy.

“The 5-year follow-up data are the longest follow-up with checkpoint inhibitors we have in MCC. Overall, [this small population represented] meaningful and important data, which established checkpoint inhibitors as the standard of care in MCC,” noted D’Angelo. 

Checkpoint inhibitors have found success in the treatment of metastatic MCC, but the question of their durability after therapy cessation was evaluated in a multicenter, international retrospective study in 40 patients.

 Avelumab was the primary checkpoint inhibitor in 90% of patients. The trial investigators found that patients had a median time on treatment of 13.5 months and median time on treatment after best response of 8 months. At the time of treatment discontinuation, a CR was achieved in 75% of patients, a partial response (PR) in 20%, and stable disease (SD) in 5%. However, after 12 months of follow-up after therapy discontinuation, 35% of patients had PD. Patients who achieved a CR had a decreased risk of relapse compared with non-CR patients (P = .044). However, PD occurred in 26% of patients who achieved a CR, in 57% who achieved a PR, and in 100% who achieved SD. A lower number of checkpoint inhibitor cycles received was associated with a risk of disease progression (P > .05); however, duration of treatment after best response was not associated with PD. The response rate to retreatment with checkpoint inhibitors was 75% in 8 of 14 patients who had PD.

D’Angelo said, “This study asks a very important question of what the consequences are of stopping therapy. My takeaway from this study is that it’s a retrospective study so there are [limitations based on its design,] but these are the best data that exist in MCC and they’re valuable and very important data. Interestingly, the response rate to retreatment was 75%. If [therapy is stopped and the disease progresses], you can recapture a lot of those responses at the time of retreatment. These are small numbers and retrospective [data], so you have to be cautious with how you interpret and utilize that data. [In clinical practice], it’s all about having conversations with patients and fi guring out what’s important to them.” 

Ongoing trials currently recruiting patients with MCC include the MERKLIN 1 (NCT04874831) and MERKLIN2 (NCT04393753) studies. MERKLIN 1 is a phase 2, open label, multicenter study evaluating the use of domatinostat, an oral class 1 HDAC inhibitor, in combination with avelumab in treatment-naïve patients with metastatic disease.

 MERKLIN2 is a phase 2, open label, multicenter, single-arm study evaluating the combination of domatinostat with avelumab in metastatic disease after progression on anti–PD-L1 antibody therapy. A total of 40 patients are expected to be enrolled in the MERKLIN2 trial.

 “These are important studies and ones that are currently enrolling, and I look forward to seeing these results,” D’Angelo said. 

Other novel therapies being explored in MCC are transgenic T-cell receptor therapy and toll-like receptor agonists. Cavrotolimod, a spherical nucleic acid consisting of toll-like receptor 9 agonists, was recently designated as an orphan drug for the treatment of MCC based on preliminary results of a phase 1b trial.

 These results demonstrated potential activity with cavrotolimod in combination with pembrolizumab with no serious toxicity concerns. Cavrotolimod in combination with pembrolizumab will be evaluated in the phase 2 dose expansion phase in 2 patient cohorts, one with advanced or metastatic MCC and the other with advanced or metastatic CSCC.

“Cavrotolimod requires intratumoral injection and the goal with all these approaches is to figure out ways to modify the immune microenvironment,” D’Angelo said. “I think the important question here is that we still don’t have good biomarkers of response to checkpoint blockade…. As a field, it’s really on us to…understand it better [which would] allow us to choose the right strategy but it seems that some sort of combinatorial strategy is where the field is headed,” she said. 

Looking at the progress and future of targeted treatment in NMSC, Wong said, “The biggest unmet need now is in the PD-1–refractory space in skin cancer. The majority of patients do not achieve a longterm response and that’s unfortunate. The question is why? All these [novel treatment approaches] are percolating and it’s an incredibly exciting time. We will see the dominant hypothesis emerge and I’m not sure what it’s going to be. The recent drug approvals in melanoma tell us there are checkpoints yet to be discovered which may be effi cacious, so that whole area with second- and third-generation checkpoint inhibitors in the field is exciting now. What I tell patients is that there are opportunities and hope in [advanced and metastatic NMSC] where in the past this was an area that was one of the dark corners of oncology. For the first time we really see a glimmer of hope and what the hope is for not just response, but long-term, unmaintained, high-quality responses, which in layman’s terms translates to cure.”

1. Villani A, Potestio L, Fabbrocini G, Scalvenzi M. New emerging treatment options for advanced basal cell carcinoma and squamous cell carcinoma. Adv Ther. 2022;39(3):1164-1178. doi:10.1007/s12325-022-02044-1

2. Migden MR, Chandra S, Rabinowits G, et al. CASE (CemiplimAb-rwlc Survivorship and Epidemiology) study in advanced cutaneous squamous cell carcinoma.Future Oncol. 2020;16(4):11-19. doi:10.2217/fon-2019-0762

3. Rohaan MW, Duizer ML, Devriese LA, Wilgenhof S, Van Herpen CM, Haanen JBA. Real-world data on clinical outcome and tolerability in patients with advanced cutaneous squamous cell carcinoma treated with cemiplimab in the Netherlands. Ann Oncol. 2021;32(suppl 5):S884-S885. doi:10.1016/j.annonc.2021.08.1447

4. Ruiz E, Chen CI, Zimmerman NM, Konidaris G, SongX.Real-world treatment patterns and outcomes of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) in the US. Ann Oncol. 2021;32(suppl 5):S885. doi:10.1016/j.annonc.2021.08.1448

5. FDA approves expanded indication for Merck’s Keytruda (pembrolizumab) in locally advanced cutaneous squamous cell carcinoma (cSCC). News release. Merck. July 6, 2021. Accessed April 8, 2022. https://www.merck.com/news/fda-approves-expanded-indication-for-mercks-keytruda-pembrolizumab-in-locally-advanced-cutaneous-squamous-cell-carcinoma-cscc/

6. Marin-Acevedo JA, Withycombe B, Kim Y, et al. Efficacy of cetuximab after immunotherapy (IO) in advanced cutaneous squamous cell carcinoma (CSCC). J Clin Oncol. 2021;39(suppl15):9562. doi:10.1200/JCO.2021.39.15_suppl.9562

7. Munhoz RR, De Camargo VP, Marta GN, et al. CA209-9JC: aphase IIstudy of first-line nivolumab (NIVO) in patients (pts) with locally advanced or metastatic cutaneous squamous cell carcinoma. J Clin Oncol. 2020;38(suppl 15):10044. 

8. Cowey CL, Chen CI, Aguilar KM, et al. Outcomes in patients (pts) with advanced basal cell carcinoma (aBCC) who discontinued hedgehog inhibitors (HHI) as first-line (1L) systemic treatment (Tx) in a U.S. community oncology setting: aretrospective observational study. J Clin Oncol. 2021;39(suppl15):e18742. doi:10.1200/JCO.2021.39.15_suppl.e18742

9. FDA approves cemiplimab-rwlc for locally advanced and metastatic basal cell carcinoma. FDA. February 9, 2021. Accessed April 8, 2022. Included in per protocol analysis (n=25)•Excluded from analysis due to compliance <705 with treatment (n=1)•Excluded from analysis due to lack of refrigeration of study medication(n=1) https://bit.ly/3JTtg5t

10. Kilgour JM, Shah A, Urman NM, et al. Phase II open-label, single-arm trial to investigate the efficacy and safety of topical remetinostat gel in patients with basal cell carcinoma.Clin Cancer Res. 2021;27(17):4717-4725. doi:10.1158/1078-0432.CCR-21-0560

11. Nghiem P, Bhatia S, Brohl AS, et al. Avelumab in patients with previously treated Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after more than five years of follow up. J Clin Oncol. 2021;39(suppl15):9517. doi:10.1200/JCO.2021.39.15_suppl.9517

12. Weppler AM, Da Meda L, Silva I. et al. Durability of response to immune checkpoint inhibitors (ICI) in metastatic Merkel cell carcinoma (mMCC) after treatment cessation. J Clin Oncol. 2021;39(suppl15):9543. doi:10.1200/JCO.2021.39.15_suppl.9543

13. Ascierto PA, van Akkooi ACJ, Nghiem P, Hermann F, Henneberg JP, Becker JC. A phase II, open label, multicenter study to investigate the efficacy and safety of domatinostat in combination with avelumab in patients with treatment-naive metastatic Merkel cell carcinoma:the MERKLIN 1 study. Ann Oncol. 2021;32(suppl 5):S901-S902. doi:10.1016/j.annonc.2021.08.1475

14. Van Akkooi ACJ, Ascierto PA, Nathan PD, et al. A phase II, open-label study to investigate the efficacy and safety of domatinostat in combination with avelumab in patients with advanced unresectable/metastatic Merkel cell carcinoma progressing on anti-PD-(L)1 antibody therapy: the MERKLIN 2 study. J Clin Oncol. 2021;39(suppl15):TPS9592. doi:10.1200/JCO.2021.39.15_suppl.TPS9592

15. Exicuregranted orphan drug designationby the U.S. Food and Drug Administration for cavrotolimod. News release. Exicure, Inc.March 3, 2021. Accessed March 29, 2022.https://bit.ly/3rKJHL9

Articles

New and emerging treatment modalities for advanced nonmelanoma skin cancer provide hope for this patient subset.

Immunotherapy Offers Hopeful Outcomes in Nonmelanoma Skin Cancers

Several notable trials in colorectal cancer suggest a shift in treatment management, especially in the length of treatment with immunotherapies. These trials were presented at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in January. 

One of the potentially clinically meaningful trials was an update to the phase 2 GERCOR NIPICOL trial (NCT03350126). GERCOR NIPICOL evaluated the efficacy of 1-year duration of immune checkpoint inhibitors (ICIs) for patients with microsatellite instable (MSI)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC).

Participants had previously progressed on chemotherapy and received nivolumab (Opdivo) plus ipilimumab (Yervoy) then single-agent nivolumab (n = 57). Thirty-six patients completed 1 year of therapy (FIGURE1). Extended follow-up results to the original data included 1-, 2-, and 3-year progression-free survival (PFS) rates of 75.4%, 70.0%, and 70.0%, respectively. Overall survival (OS) rates at 1, 2, and 3 years were 84.1%, 78.4%, 73.1%, respectively. Follow-up data for 1 year of fixed-duration therapy with ICIs demonstrated durable responses in patients with MSI/dMMR mCRC.

“What [the investigators] reported was quite interesting and impressive. I think a very important message is maybe after 1 year of therapy, if the disease has responded or is nonprogressive by imaging, we can maybe stop treatment,” said Afsaneh Barzi, MD, PhD, an associate professor of GI oncology at City of Hope Comprehensive Cancer Center in Duarte, California, and director of employer strategy at AccessHope, in an interview with 

™. “In a few patients who had recurrence, [rechallenge] with the same treatment with an ICI demonstrated a benefit. We all know the [safety] profile of an ICI is different from chemotherapy. Although chemotherapy [adverse events] such as nausea and vomiting are transient, [adverse events] of immunotherapy, [such as] hypothyroidism, can last a lifetime. Getting patients off therapy appropriately is important. Another perspective on this is the financial toxicity….If there is a subset of patients who can safely stop this treatment, it not only reduces the chance of physical toxicities experienced by them, but it also reduces the chance of financial toxicities. I thought this abstract was meaningful with positive implications for practice.” 

Cathy Eng, MD, FACP, FASCO, the David H. Johnson Chair in Surgical and Medical Oncology, codirector of GI oncology, and coleader of the GI Cancer Research Program at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, agreed. “It was refreshing to see that maybe just 1 year [of ICI therapy] is enough. [ICIs and duration of use are] just so new in colorectal cancer for our MSI-high patients. It wasn’t a large study, but it was intriguing. It brings to light the question of duration,” she said in an interview with 

Another notable trial presented was a phase 1/2 single-arm, single-institution study (NCT04017650) that evaluated patients with treatment-refractory, microsatellite-stable (MSS), 

 mutation [occurs] in less than 10% of patients and tends to be microsatellite stable; [it is] a very aggressive tumor type.” Patients with MSS, 

 V600E–positive mCRC may benefi t from combination therapy with encorafenib (Braftovi), cetuximab (Erbitux), and nivolumab therapy, the study results showed.

Of 26 patients enrolled, 21 were evaluable for response. The overall response rate (ORR) was 45% and disease control rate (DCR) was 95%.2 “We all know that encorafenib and cetuximab [are] the standard of care in 

-mutated CRC in the second and subsequent lines of therapy. [The response rate] is significant compared with the response rate of [approximately] 20% in encorafenib and cetuximab,” Barzi said. Safety results included zero dose-limiting toxicities. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 18% (n = 21) and consisted of colitis, maculopapular rash, leukocytosis, and others.

“This study provides potential treatment for 

-mutated cancer, which has very poor prognosis, and this may be the only subset of the MSS colorectal cancer population that would derive some benefi t from the addition of nivolumab to the targeted therapy backbone,” Barzi said. Eng said that the multicenter phase 2 trial to further explore this combination therapy “should be open very soon and that’s encouraging…. The data will be validated in a larger subset in SWOG 2107.” 

The role of ICIs in CRC is currently being explored in different patient populations. Dostarlimab (Jemperli), a PD-1 inhibitor with benefit in dMMR advanced solid tumors after prior therapy, was evaluated in an open-label, multicenter, single-arm, phase 1 trial (NCT02715284).

 A subgroup of cohort F included patients with dMMR/MSI-high CRC or patients with 

ε-mutated CRC. Confirmed ORR was 36.2% in patients with CRC (n = 69). TRAEs in the dMMR nonendometrial solid tumor cohort F occurred in 68.1% of patients (n = 141). The most common TRAE grade 3 or higher was increased lipase (1.4%). No new safety concerns were noted with dostarlimab in cohort F, and efficacy results were consistent with non-CRC populations.

Another trial (SPRINT; NCT04256707) evaluating the use of immunotherapy in CRC was the open-label phase 1/2 trial in MSS, 

-mutated, pretreated, advanced, or mCRC, which investigated the use of selinexor (Xpovio) with pembrolizumab (Keytruda).

 Selinexor selectively inhibits nuclear export and has demonstrated activity in 

 mutation in combination with PD-1/PD-L1 inhibition. In patients with 

-mutated CRC, the best overall response was stable disease in 62% (n = 13). Stable disease was achieved as the best overall response in 25% of 

 wild-type (WT) CRC (n = 12). Median PFS was longer in patients with CRC with 

 mutations (3.0 months) compared with patients with 

 WT mutations (1.4 months; P = .04). Common treatment-emergent AEs included nausea, vomiting, fatigue, decreased appetite, and diarrhea.

Also presented at the symposium were some notable negative trials. Regorafenib (Stivarga) combined with pembrolizumab (Keytruda) was evaluated in patients with MSS CRC in a multicenter phase 1/2 trial (NCT03657641).

 Liver metastases were identifi ed in 78% of patients at baseline (n = 73), and their median PFS was 2.0 months and median OS was 10.9 months. Median PFS in patients with nonliver metastatic disease was 4.3 months (n = 16). Common grade 3 toxicities were rash, hand-foot syndrome, and hypertension.

“The study was considered positive if the prespecified median PFS of 2.85 months was achieved; this benchmark is a significant improvement over the PFS of single-agent regorafenib. Unfortunately the study failed to show improvement in PFS,” Barzi said. “However, I think in every negative study there are lessons to be learned. The potential lessons of this study are, No. 1, we do not want to use the combination of regorafenib with ICIs in [patients with MSS CRC] outside of trials because we don’t have evidence of any efficacy…from this trial and a number of other trials already presented. No. 2 is that in the overall study population, this [treatment] was not effective, but a post hoc analysis identified 2 groups of patients with potential benefit—those who received prior radiation therapy and those who had nonliver metastases. We have an extensive biomarker analysis that’s planned, and we are hopeful that in the future we can record biomarkers or unique clinical characteristics that identify the subset of patients who may benefi t from this treatment.” 

Another negative trial was in patients with 

 WT mCRC, a multicenter, single-arm, Simon 2-stage phase 2 trial (NCT03446157) that evaluated cetuximab and palbociclib (Ibrance) in patients with at least 2 prior treatment regimens.

 Results from cohort B demonstrated a 4-month DCR of 20% (n = 10). However, enrollment was stopped based on the DCR not meeting prespecified criteria from the fi rst stage. Enrollment for cohort A with patients who were anti–EGFR naïve is ongoing.

“We’ve had a lot of negative studies in CRC and yes, it looks disappointing,” Barzi said. “We should look at it as our learning opportunity and hopefully [we] are putting all of these lessons into action.…I believe all of what we have and will learn are propelling us toward new treatments, new paradigms, and new ways to treat patients with CRC.” 

Another genomic alteration being explored in CRC is 

 A real-world exploratory analysis of prevalence of 

 alterations using next-generation sequencing (NGS) was assessed using 7688 deidentified records from patients with CRC.

Results demonstrated 5% of tumors consisted of

 amplification occurred in 1.9% of tumors (n = 143) whereas 1.3% of tumors were 

 mutated (n = 97) and 0.9% of tumors were 

 alterations were associated with MSI high (P < .001) and tumor mutational burden (TMB) high (P < .001), compared with 

 WT were significant and may be further explored to guide the development of HER2-targeted therapies.

“It looks like the [overall] progress in [research in] CRC is a slow one in that we’re not identifying new therapies [compared with other solid tumors],” Barzi said. “However, we must take a step back and look at it a different way, and that is that CRC is a disease that is fairly chemotherapy sensitive… thus it is hard to identify therapies that can beat the very effective chemotherapy that exists for this disease. In oncology, I don’t think we should always look for new therapies. Optimization of current therapies is actually one of the important things that we should focus on or work on in the field, and we are seeing some of that optimization in recent years.” 

Looking to the future of treatment on CRC, Eng said, “We are trying to become more intelligent with how we approach our patients with sequencing, impact on quality of life, looking at new tools such as circulating tumor DNA in our [patients with early-stage cancer] and the risk of recurrence, which impacts how patients undergo surveillance. Additionally, we need to do a better job with clinical trial enrollment. We cannot get any new drug advances unless patients participate in clinical trials.”

1. Cohen R, Meurisse A, Pudlarz T, et al. One-year duration of nivolumab plus ipilimumab in patients (pts) with microsatellite instability-high/mismatch repair-defi cient (MSI/dMMR) metastatic colorectal cancer (mCRC): long-term follow-up of the GERCOR NIPICOL phase II study. J Clin Oncol. 2022;40(suppl 4):13. doi:10.1200/JCO.2022.40.4_suppl.013 

2. Morris VK, Parseghian CM, Escano M, et al. Phase I/II trial of encorafenib, cetuximab, and nivolumab in patients with microsatellite stable, BRAFV600E metastatic colorectal cancer. J Clin Oncol. 2022;40(suppl 4):12. doi:10.1200/JCO.2022.40.4_suppl.012 

3. Andre T, De Braud FG, Jimenez-Rodriguez B, et al. Antitumor activity and safety of dostarlimab monotherapy in patients with mismatch repair defi cient non-endometrial solid tumors: a post-hoc subgroup analysis of patients with colorectal cancer. J Clin Oncol. 2022;40(suppl 4):201. doi:10.1200/JCO.2022.40.4_suppl.201 

4. Golan T, Kutiel TS, Gottfried M, et al. Open-label phase 1/2 study evaluating the tolerability and antitumor activity of selinexor and pembrolizumab in colorectal cancer. J Clin Oncol. 2022;40(suppl 4):110. doi:10.1200/JCO.2022.40.4_suppl.110 

5. Barzi A, Azad NS, Yang Y, et al. Phase I/II study of regorafenib (rego) and pembrolizumab (pembro) in refractory microsatellite stable colorectal cancer (MSSCRC). J Clin Oncol. 2022;40(suppl 4):15. doi:10.1200/JCO.2022.40.4_suppl.015 

6. Sorah JD, Moore DT, Reilley M, et al. Phase II single-arm study of palbociclib and cetuximab rechallenge in KRAS/NRAS/BRAF wild-type (KRAS WT) metastatic colorectal cancer (mCRC) patients (pts). J Clin Oncol. 2022;40(suppl 4):88. doi:10.1200/JCO.2022.40.4_suppl.088 

7. Tie J, El-Refai SM, Yoshino T, et al. Genomic landscape of ERBB2/3 alterations in colorectal cancer: Comutations, immuno-oncology biomarkers, and consensus molecular subtype. J Clin Oncol. 2022;40(suppl 4):176. doi:10.1200/JCO.2022.40.4_suppl.176

Several notable trials in colorectal cancer suggest a shift in treatment management, especially in the length of treatment with immunotherapies.

Exploring Precision Medicine Approaches in Colorectal Cancer: Updates From the Gastrointestinal Cancers Symposium

Several next-generation biomarkers are currently emerging in multiple myeloma (MM) that could lead to improved clinical management and outcomes, as well as enhanced precision medicine. “There are still a lot of things that are ongoing, and the myeloma field is evolving with new treatments. It’s a very interesting time for myeloma research in general and for patients with myeloma. There is a lot of interest to understand the disease better,” said Mark Bustoros, MBBCh, assistant professor of medicine at Weill Cornell Medicine, Cornell University, and the Division of Hematology and Medical Oncology at NewYork-Presbyterian Weill Cornell Medical Center.

MM is a hematologic malignancy characterized by proliferation of abnormal plasma cells in the bone marrow. Diagnosis and risk stratification of MM depend on primary biomarkers, M protein, ß2-microglobulin, albumin, and lactate dehydrogenase.

Biomarker assessment is performed using electrophoresis, fluorescence in situ hybridization (FISH), and imaging to diagnose and risk-stratify the disease.

Biomarkers in MM also contribute to determining the stage of the disease in patients. The International Staging System (ISS) and, most recently, the Revised International Staging System (R-ISS) are used to stage patients.

The R-ISS incorporates cytogenetic abnormalities, signifying the importance of the involvement of genomics in the prognosis of patients.

Discussing the current staging system in the era of novel treatment options in MM, Bustoros said that “with the advent of the new therapies—especially the monoclonal antibodies such as daratumumab [Darzalex], chimeric antigen receptor [CAR] T, and other immunotherapies— [the relationship between the staging system and novel treatments] is in flux.”

Although there are established biomarkers for MM, novel biomarkers are needed for improved disease diagnosis and treatment.

 The complexity of the disease, along with novel treatment approaches, warrants the exploration of unique biomarkers for improving early diagnosis and optimizing response to treatment, which may lead to improved clinical management of MM and survival outcomes.

Minimal residual disease (MRD) is being assessed in clinical practice and has emerged as a pertinent and potential surrogate biomarker in MM. Patients who achieve MRD-negative status have longer progression-free survival (PFS) and overall survival (OS); therefore, MRD is a useful prognostic tool.

“We’re looking at MRD assessment in the marrow, based on sequencing of the immunoglobulin light and heavy chain genes from the malignant plasma cells at diagnosis, which are unique sequences, similar to a fingerprint...[this] serves as a really good predictor of long-term response in myeloma. I’ve been routinely sending MRD assessment on patients [who have just received diagnoses] for several years because the test is now authorized by the FDA,” said Thomas G. Martin, MD, clinical professor of medicine, associate director of the Myeloma Program at University of California San Francisco, and coleader of the Cancer Immunology & Immunotherapy Program at Helen Diller Family Comprehensive Cancer Center, also in San Francisco.

"We’re entering the immunotherapy era for treating relapsed [MM] and these novel drugs, most targeting B-cell maturation antigen (BCMA), are showing impressive early results,” Martin said. The high-specific and tissue-specific expression of BCMA on myeloma cells has quickly advanced this target and propelled the development of novel BCMA-directed therapies in myeloma.

 Additional evidence has demonstrated that soluble BCMA (sBCMA) levels may be a useful biomarker for precursor plasma cell disorders including monoclonal gammopathy of undetermined significance and smoldering MM. In a retrospective study, increased levels of sBCMA in the precursor state were associated with disease progression to active MM. Additionally, patients with higher baseline sBCMA levels had poorer PFS and OS outcomes.

Martin added, “The hard part about soluble BCMA is that there’s not a currently available CLIA [Clinical Laboratory Improvement Amendment] test. Studies are evaluating whether sBCMA can accurately predict response to therapy and may be an early marker for recurrence/progression. So far, several studies have shown that when a patient has a great response, the sBCMA levels become undetectable and when sBCMA levels become detectable, it’s a sign that the myeloma is growing back again. We are very hopeful that a CLIA test will be developed and that sBCMA will be an excellent biomarker for [MM].”

Another potential novel biomarker is the presence of the translocation t(11;14) by bone marrow FISH testing.

 “The t(11;14) translocation in myeloma is associated with the upregulation of BCL2 pathway, and thus researchers began investigating the clinical use of BCL2 inhibitors in this subset of patients,” said Martin. Patients whose myeloma cells express the t(11;14) translocation have demonstrated clinical responses to venetoclax (Venclexta).

According to Bustoros, “Until now, the only known predictive biomarker for response to therapy in a patient is having t(11;14). We know venetoclax would be a good option for [patients with t(11;14)] at relapse. It’s not [FDA] approved for up-front treatment yet.”

Looking into the future for using t(11;14) as a biomarker for drug therapy, Martin added, “There are trials going on right now using venetoclax in patients with t(11;14) and those patients do extremely well...I suspect [venetoclax] will be approved for use in patients with t(11;14) as part of frontline therapy and in relapse within the next few years.” Other exploratory biomarkers that may be associated with t(11;14) are del(17p) or gain(1q).

Other emerging biomarkers include circulating tumor cells (CTCs) and microRNAs (miRNAs). “[miRNAs] and CTCs are in early investigations in myeloma and we’re still figuring out which assays to use, and how and in which patients these bioassays may help,” said Martin. CTCs were found to be released in the peripheral blood of MM from the tumor cells in bone marrow and detected by flow cytometry.

The benefit of CTCs is the noninvasive nature of their use for detecting MM compared with a bone marrow biopsy for diagnosis.

 Additionally, the use of CTCs may be prognostic at diagnosis and they may be used in conjunction with MRD as a response biomarker.

MiRNAs are expressed on all cells and consist of short noncoding RNAs. MiRNAs are an attractive biomarker in MM due to their function as tumor promoters or suppressors. There is potential for the use of miRNAs in the diagnosis and prognosis of MM. However, more research is needed for validation of miRNA use.

 “Given the difficulties in isolating [miRNAs], detecting them, and measuring them, I would say it needs time to be translated clinically,” said Bustoros.

Other novel biomarkers that may warrant further exploration and evidence for use include proteomic and angiogenesis biomarkers. The use of proteomic biomarkers has the potential to provide diagnostic and prognostic information in patients with MM.

 Further research into proteins such as proteasome activator complex subunit 1, heat shock protein 90, and others may provide insight into how these proteins may be used as biomarkers for patients with MM in the future.

 Angiogenesis biomarkers are known to be associated with tumor cells requiring adequate blood supply for tumor growth.

 Markers associated with angiogenesis may include VEGF, hepatocyte growth factor (HGF), angiopoietins, and JUNB.

“There don’t seem to be [many] mutations that are targetable in myeloma. We do see 

 mutations, so we do see mutations in which there may be drugs that potentially could target these pathways, but there are only a few studies investigating specific mutation-driven treatment in patients with myeloma. We’re really at the infancy compared with other malignancies such as lung cancer,” said Martin.

There may be other genetic or mutationally driven treatment pathways for the future, perhaps ways to predict drug/disease resistance. The immunomodulatory [IMiD] drugs target a protein called cereblon. We’re only starting to learn about mutations in cereblon and that these mutations might predict resistance to the IMiD class of medications. Similarly, we are starting to identify deletions on chromosome 16 that are associated with BCMA loss on plasma cells,” said Martin. The efficacy of IMiDs depends on the presence of cereblon, a binding protein, and the efficacy of BCMA therapeutics depends on the surface expression of BCMA.

 Although cereblon is not a biomarker currently used in practice, it is under investigation as a promising potential marker in resistance to IMiDs.

Other potential biomarkers that may provide insight into resistance include del(17p) and gain(1q).

"We know these 2 genetic alterations are biomarkers of worse response to treatment in general,” Bustoros said. Patients harboring high-risk cytogenetics have poor prognosis regardless of treatment options.

 Bustoros also said that “[patients with del(17p) and gain(1q)] are the ones who frequently relapse and progress after multiple lines of treatment.”

There are many potential biomarkers on the horizon for patients with MM. Although the impact of research in biomarker assessment may be intangible now, a tangible change to clinical practice was discussed by Martin: For biomarker measurement, “an emerging test that’s going to be really important is mass spectroscopy of the monoclonal protein in the blood. Assessment of serum M protein by mass spectroscopy will be much more sensitive and will be able to detect a far lower level of M protein compared with the current protein electrophoresis and immunofixation electrophoresis assays. M protein quantification by mass spectroscopy may be as sensitive as some of the MRD assays from bone marrow. It’ll be a great technique to use together with bone marrow MRD and a great blood test to identify deep remissions from standard therapy as well as from some of the new novel therapies.”

Progress continues in the research and development of biomarker assessment in MM. The complexity of the disease may warrant multiple biomarkers to provide clarity on diagnosis, prognosis, and response to treatment with the goal of personalizing patient treatment to improve outcomes.

“There are a lot of evolving biomarkers and that will benefit patient treatment...integrating genetic biomarkers with biomarkers that can be measured from blood samples, bone marrow biopsies, and circulating tumor cells,” Bustoros said. “All of this would be used in the future to identify patients who would progress at very early time points. I think biomarkers would be very important to tailor therapy for specific patients...the sequence of treatment also would benefit from understanding the biomarkers and knowing the biomarkers of response.”

1. Gupta N, Sharma A, Sharma A. Emerging biomarkers in multiple myeloma: A review. Clin Chim Acta. 2020;503:45-53. doi:10.1016/j. cca.2019.12.026
2. Soliman AM, Das S, Teoh SL. Next-generation biomarkers in multiple myeloma: understanding the molecular basis for potential use in diagnosis and prognosis. Int J Mol Sci. 2021;22(14):7470. doi:10.3390/ijms22147470

3. Wallington-Beddoe CT, Mynott RL. Prognostic and predictive biomarker developments in multiple myeloma. . 2021;14(1):151. doi:10.1186/s13045-021-01162-7


4. Visram A, Soof C, Rajkumar SV, et al. Serum BCMA levels predict outcomes in MGUS and smoldering myeloma patients. Blood Cancer J. 2021;11(6):120. doi:10.1038/s41408-021-00505-4

5. Kaufman JL, Gasparetto C, Schjesvold FH, et al. Targeting BCL-2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma. Am J Hematol. 2021;96(4):418-427. doi:10.1002/ajh.26083

6. Gooding S, Ansari-Pour N, Towfic F, et al. Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma. Blood. 2021;137(2):232-237. doi:10.1182/blood.2020007081

7. Bustoros M, Mouhieddine TH, Detappe A, Ghobrial IM. Established and novel prognostic biomarkers in multiple myeloma. Am Soc Clin Oncol Educ Book. 2017;37:548-560. doi:10.1200/EDBK_175175

There are still a lot of things that are ongoing, and the myeloma field is evolving with new treatments, according to Mark Bustoros, MBBCh.

Evolving Biomarkers Span Proteomic, Genomic Fields in Multiple Myeloma

Nanotechnology is a rapidly evolving treatment modality in oncology.

 Nanotechnology advances in oncology have applications in diagnosis, biomarker screening, and most notably, treatment. Conventional chemotherapy has been the mainstay of oncology treatment; however, due to its indiscriminate mechanism of inducing cytotoxicity, multiple undesired toxicities are experienced.

 Compared with conventional chemotherapy, nanotechnology has the potential to be precise and effective in selecting for tumor cells with a reduction in undesired adverse events (AEs) on normal tissue, making this novel approach a promising treatment in cancer.

Nanoparticles are defined as particles with a size of 1 to 100 nm.

 The optimal diameter range to achieve enhanced permeability and retention (EPR) effects is 10 to 100 nm for best drug delivery.

 Nanoparticles can be composed of organic, inorganic, and hybrid material.

Organic nanoparticles include liposome and polymer-based compositions. Inorganic nanoparticles include gold, carbon nanotubes, silica, magnetic, and quantum dots. Inorganic nanoparticles have higher surface area to volume ratio with an easily modifiable surface conjugation chemistry; however, its biocompatibility and biodegradability is not as robust as organic nanoparticles. Within inorganic nanoparticles, silica nanoparticles are favorable carriers for drug delivery due to its pharmacokinetics, treatment efficacy, and high stability.

Hybrid nanoparticle composition may include lipid-polymer, organic-inorganic, and cell membrane-coated.

 In drug delivery, passive targeting of tumor cells using nanotechnology relies on the size of the nanoparticle to be retained by cancer cells with poor lymphatic drainage. Alternatively, using ligands on the surface of nanoparticles to directly target tumor cells is a modality in active targeting.

“Nanotechnology is a rather big field and it is a broad field. There are many people working on trying to focus on using nanoparticles for clinical application in oncology,” Maciej Lesniak, MD, at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, said during an interview with 

Lesniak, the Michael J Marchese Professor and Chairman, Department of Neurological Surgery, at Northwestern University Feinberg School of Medicine in Chicago, and program leader in Neuro-Oncology at Northwestern, was an investigator evaluating the use of spherical nucleic acids (SNAs). The SNA is a type of oligonucleotide, such as small interfering RNA (siRNA), which surrounds a nanoparticle core. The nanoparticle core can be made from gold, silver, iron oxide, quantum dots, platinum, silica, core-shell, and liposomes.

In this particular study, SNAs containing siRNA oligonucleotides on gold nanoparticle cores were used to target BCL2L12, a protein coding gene, for the treatment of recurrent glioblastoma.

 There were 8 patients enrolled with the study agent, NU-0129, administered intravenously 24 to 28 hours prior to tumor resection and tissue analysis. Grade 3 or higher AEs potentially related to administration of NU-0129 were hypophosphatemia and lymphopenia, the investigators reported. Only 6 of 8 tumor resections were analyzed due to tissue sample size.

“We were able to show that peripheral injection of the gold nanoparticles actually achieves distribution within the brain and the tumor itself and that it seems to downregulate [one of the key] proteins within the tumor itself,” Lesniak said. Results demonstrated gold nanoparticle accumulation in tumor-associated endothelium in tumor- associated macrophages and Ki67-positive tumor cells.4 Downregulation of BCL2L12 protein signified drug penetration of the blood brain barrier and accumulation in tumor cells. Acute and long-term toxicities of NU-0129 were not experienced in patients.

Gold Nanoparticles Gold nanoparticles are an attractive treatment option because it can be used for gene therapy, photothermal therapy, and immunotherapy.2 Gold nanoparticles can be used to decrease the time of disease metastasis by increasing nuclear membrane stiffness. It may be modified to contain methoxy-polyethylene glycol thiol (PEG), RDG peptides, and nuclear localization signal peptides. The tumor cells absorb the gold nanoparticles and subsequently cause nuclear stiffness of the cancer cell to decrease the rate of metastasis of cancer cells.

In addition to gold nanoparticles, other metals have been used in combination with magnetic fields.

 Magnetic nanomaterials is a therapeutic option that has demonstrated promising results.6 The advantage associated with magnetic nanomaterials is the destruction of cancer cells via hyperthermia and mechanical force, providing an alternative to chemotherapy. Additionally, a magnetic field may be used to initiate specific signaling pathways to cause tumor cell lysis without contact. In a study evaluating the effects of magnetic nanoparticles on glioma in mice implanted with U87 glioma cells. Treatment involving rotating magnetic fields were provided daily to the treatment group.

“We looked at using magnetic nanoparticles that oscillate upon application of external fields. When you bind these nanoparticles to cancer cells, just the gentle oscillation disrupts the cancer cell membrane … and therefore mechanical destruction of cancer cells,” Lesniak, an investigator in the trial, said.

The treatment group achieved tumor regression by day 7 whereas the control group had tumor growth.

 Additionally, by day 28, 40% of the treatment group demonstrated effective treatment strategy with effective tumor growth inhibition. Long-term tumor growth suppression was also observed in 40% the treatment group with long-term survival benefit. The results from this study provided a different modality in treating glioma with mechanical force. Another advantage demonstrated from the study with the use of magnetic field is the level of penetration to the tumor cells without damaging other biological tissues.

On the advantages of nanotechnology, Lesniak said, “the advantages are obvious. There is an intellectual, intrigue component to these nanoparticles [and their potential use]. There’s an element of excitement about nanoparticles and its applicability in the form of cancer.”

The versatility of nanoparticles allows for its application with multiple oncology treatments including, chemotherapy, targeted therapy, radiotherapy, hyperthermia, gene therapy, and immunotherapy.

 Due to the properties of nanoparticles, self-assembly, stability, and specificity are advantages of its use, allowing for interactions with tumor cells and the tumor microenvironment with improved specificity compared with chemotherapy.

Other benefits thought to derive from nanotechnology is the ability to enhance immunotherapy and reverse the tumor immunosuppressive microenvironment.2 Furthermore, nanotechnology may be used to overcome multidrug resistance, especially with hybrid nanoparticles using multiple chemotherapy agents within the carrier. There have been reports of nanoparticles overcoming multidrug resistant tumors in breast cancer, ovarian cancer, and prostate cancer.

Alternatively, Lesniak said, “the biggest challenges [with nanotechnology] have to do with the manufacturing and preclinical development. For instance, gold [nanoparticles] work great in some preclinical models and in vitro. However, it’s somewhat difficult to execute in human trials simply because of the cost associated with producing gold nanoparticles. Most [investigators] start switching to lipid nanoparticles or other chemical formulations that would allow scalability and would therefore decrease the cost associated with the production that would be necessary to enroll a large number of patients.”

Lesniak also commented that another notable challenge with nanoparticles is the effects on the rest of the organ systems. Nano-bio interactions is complex with preclinical data demonstrating only 0.7% of injected nanoparticles accumulating in tumors.

 “We need more human clinical trial work, especially in cancer, to [understand when nanoparticles are cleared from the body], how they are cleared, and the [clinical implications]. We always want to balance therapy with preventing harm to organs and this is a challenge. It is an area of active investigation,” Lesniak said.

Due to the practicality, the majority of nanoparticles is in the form of liposomes.

 Liposomes are spherical nanoparticles with an outer lipid layer mimicking human cells enclosed around an aqueous center, which may contain chemotherapy and nucleic acids.

 One of the successful clinical applications of liposomes is with liposomal doxorubicin.4 Due to the nanoparticle system, liposomal doxorubicin has demonstrated less cardiotoxicity compared with conventional doxorubicin. Likewise, nanoparticle albumin-bound paclitaxel also exhibits less AEs compared with conventional paclitaxel, achieving the goal of decreased toxicity with nanoparticle use.

Drug Design Lesniak commented on how to incorporate nanotechnology into drug design. “These translational studies that go from bench to bedside where we develop a clinical grade agent, work with FDA to get [approval and an infrastructure that is compliant with regulatory issues] and test it in early stage clinical trials patients, whether it’s gene therapy or nanoparticle protocols, involves a team approach in working with a disease for which there is an unmet need.”

Current and future work in nanotechnology may include “looking at the immunomodulatory function and how to use nanoparticles to enhance the immune system to fight cancer,” said Lesniak. Furthermore, he stated, “one area where I see [nanotechnology] potentially making a big dent is in terms of imaging micrometastases. Thinking about how we can detect smaller tumor burdens in the order of one thousand cells instead of a mass of millions of cells is a really important thing when it comes to metastases. We can then treat those [micrometastases] with targeted radiotherapy or chemotherapy [using nanotechnology].”

Although nanotechnology in the treatment of cancer has tremendous potential, the clinical implications have yet to be fully manifested. Overcoming the nano-bio barriers in a team approach to utilize advanced disease modeling, omics technologies, computing, and using artificial intelligence may accelerate the research and translational medicine into successful clinical settings.

 “We still have a ways to go and I think the incredible people around the world, including this country, will pave the way for the future,” Lesniak concluded.

1. Jin C, Wang K, Oppong-Gyebi A, Hu J. Application of nanotechnology in cancer diagnosis and therapy - a mini-review. 

. 2020;17(18):2964-2973. doi:10.7150/ijms.49801 

2. Yao Y, Zhou Y, Liu L, et al. Nanoparticle-based drug delivery in cancer therapy and its role in overcoming drug resistance. 

. 2020;7:193. doi:10.3389/fmolb.2020.00193 

3. Leng F, Liu F, Yang Y, Wu Y, Tian W. Strategies on nanodiagnostics and nanotherapies of the three common cancers. Nanomaterials (Basel). 2018;8(4):202. doi:10.3390/nano8040202 

4. Wang X, Yang L, Chen ZG, Shin DM. Application of nanotechnology in cancer therapy and imaging. CA Cancer J Clin. 2008;58(2):97-110. doi:10.3322/CA.2007.0003 5. Kumthekar P, Ko CH, Paunesku T, et al. A first-in-human phase 0 clinical study of RNA interference-based spherical nucleic acids in patients with recurrent glioblastoma. 

. 2021;13(584):eabb3945. doi:10.1126/scitranslmed.abb3945 

6. Cheng Y, Muroski ME, Petit DCMC, et al. Rotating magnetic field induced oscillation of magnetic particles for in vivo mechanical destruction of malignant glioma. 

. 2016;223:75-84. doi:10.1016/j.jconrel.2015.12.028 

7. de Lázaro I, Mooney DJ. Obstacles and opportunities in a forward vision for cancer nanomedicine. 

. 2021;10.1038/s41563021-01047-7. doi:10.1038/s41563-021-01047-7

Nanotechnology advances in oncology have applications in diagnosis, biomarker screening, and most notably, treatment. 

Thao K. Adams, PharmD, BCOP | Authors

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