2026 AACR Report Highlights Advances and New Directions in Cancer Treatment

Advances in cancer research continue to expand treatment options and create new opportunities to detect disease earlier. Emerging therapies and technologies are also reshaping how clinicians approach treatment decisions, with the potential to improve outcomes across cancer types.

In an interview with Targeted Oncology^TM, Keith Flaherty, MD, director of clinical research at the Massachusetts General Hospital Cancer Center, professor of medicine at Harvard Medical School, and president of the American Association for Cancer Research (AACR), discussed key treatment and technological developments highlighted in the AACR Cancer Progress Report 2026 and how these advances could shape the future of cancer care.

This is part 2 of a 2-part interview. Read part 1.

Targeted Oncology: What treatment advances are having the most meaningful impact on clinical decisions today?

Keith Flaherty, MD: If you focus on this past year…there have been 11 new approvals for new cancer therapies, and nearly all of those were in the category of molecularly targeted therapy.¹ We’ve obviously been realizing gains there for about 20 years now, but the pace of progress has continued to pick up in terms of identifying molecular drivers of disease, biomarker-defined populations, and developing very specific therapies for those populations, so matching a diagnostic or a therapeutic. Although that’s not a new story, if you look at the trajectory and the number of approvals, I would say that’s an easy first answer to the question of what’s been increasingly impactful, and particularly in this past 1-year interval.

Within that domain, we are just now starting to see some of the chemistry advances that have been made in the past several years now translating to therapies, many of which are in clinical trials, but one of which made it across the finish line to FDA approval in this past year. That’s a PROTAC [proteolysis targeting chimera], a molecule that basically targets and degrades its molecular target. This is a class of molecules that has [become broadly applicable] across the spectrum of cancer types and molecular targets. To see one of those now make it to the finish line with so many others behind it in clinical trials gives us a lot of hope that that type of chemistry advance is going to represent a substantial step-function gain in the types of targeted therapies that we’re able to deliver and the types of targets that we can go after.

Of course, I shouldn’t skip over a huge advance that again comes from a chemistry breakthrough, and that’s the first of the KRAS-targeted drugs, which is not a top-secret event. Daraxonrasib [Rasonque], which targets all forms of RAS whether mutated or not, doubles survival in patients with metastatic pancreatic cancer, a cancer type where we’ve never seen that type of improvement with any of our historical attempts. Importantly, across cancer, about 25% of patients have KRAS mutations;² in nearly all patients with pancreatic cancer, tumors harbor a KRAS mutation,³ and for the longest time, we thought we were never going to see a day where we would be able to directly target RAS with drugs. While that’s a milestone in terms of improving survival and leading to FDA approval just after this report was published, but the positive phase 3 result we knew about within the frame of this report, there’s a whole pipeline of KRAS drugs of different sorts that are in clinical trials, but many of which have clinical data already presented. We think this is going to move the needle for that entire group—one-quarter of all patients with cancer. So that’s a big deal, and I think points toward that the idea that we have not exhausted the molecular targeted therapy category.

I would also sneak in that we finally saw a PD-1 antibody move the needle in ovarian cancer and reach FDA approval. PD-1 antibodies had been racking up approvals now for over a decade, and about 60% of all patients with cancer at this point have a cancer type for which PD-1 antibodies are approved.¹ Ovarian cancer was a late addition to that spectrum of cancer types, and so that was a gratifying result. If you back up to the entire population of patients with advanced cancer, about 10% receive a PD-1 antibody and have remarkably durable clinical benefit—some of them we even think [have a] curative outcome, even when they started with metastatic disease.¹

Lastly, cell therapy or CAR [chimeric antigen receptor] T-cell therapy, which has been found to be reproducibly effective in hematologic cancers of certain kinds, is now approved for another lymphoma type, marginal zone lymphoma. That’s another milestone in CAR T applicability, at least in the hematologic cancer space.

Which of the emerging technologies mentioned in the report are closest to having a meaningful impact on practice that oncologists be keeping their eye on?

I think the here-and-now answer is blood-based measurements of circulating tumor DNA [ctDNA]. That’s a technology in development for over several years now, but its deployment and our understanding of the benefits of using it in clinical practice are escalating. I would say what’s not new is the idea of using blood-based assessment of ctDNA to understand the genetic profile of a patient’s cancer when it’s technically challenging or not safe to perform a biopsy for a patient who’s had recurrent cancer. So, where there’s something potentially to biopsy, but the size of a lesion or its location doesn’t lend itself to a neo-biopsy approach, the concept of using ctDNA tests in that setting is reasonably established, I think, although there’s room for improvement there with better technologies.

I think the bigger issue is using these tests to detect residual cancer in settings where historically, we’ve not been able to discern whether a patient does still have cancer, particularly after definitive therapy—surgery with or without radiation, depending on the tumor type—and then even after receipt of conventional adjuvant therapy for cancers for which we have evidence-based adjuvant treatments. For these ctDNA assays that have become increasingly sensitive, we now have evidence from multiple studies that they can find a meaningful fraction of those patients who are destined to have their cancer recur soon after their initial diagnosis and definitive therapy. There are certain cancer types where we still don’t have standard adjuvant therapy, so it can be as soon as the completion of surgery and, of course, radiation treatment if indicated, that you can then now much better sort patients into those who actually still have the problem of cancer vs those who likely don’t, but are not assured of that. That’s an important breakthrough because it’s going to allow us to concentrate our efforts in terms of not only applying the therapies that we have but also investigating new therapies and even “escalating” therapy in these patients who have persistent evidence of cancer in the blood only, but no radiographic or clinical evidence. That’s one of the technology approaches that many of us think is going to allow us to start to shift the deployment of a lot of our therapeutic armamentarium to a much earlier point in the cancer disease course. We’ve often thought about the introduction of new therapies in clinical trials and clinical practice in patients whose treatments have failed them in the metastatic setting, but increasingly we’re seeing an opportunity to think about deploying therapies, even when there’s not yet radiographic or clinical evidence. So, there’s been a big thrust of recent evidence generation for ctDNA for minimal residual disease detection, and these tests are available. In clinical practice, I think practitioners need to try to keep their finger on the pulse of, in which cancer types are these approaches best validated, and then, what would you do with a positive result in terms of orchestrating treatment for those patients? That’s a work in progress because we have a lot of ongoing trials that are trying to sort that out but that’s a ready-for-prime-time technology, I would say.

Multicancer early detection, of course, comes before the oncologist. We’re seeing advances there also; it’s a progression of similar tests that we’re using for minimal residual disease, but there are some important differences technologically. There’s a lot of room for improvement in terms of better sensitivity and detection of early cancer. If we can localize a primary tumor and intervene with surgery at earlier cancer stages, we think that could ultimately be hugely impactful, but it’s just in the very early days in terms of those technologies demonstrating enough ability to detect cancer early.

What do you think will be the most important shift in how cancer treatment is approached over the next 5 to 10 years?

We’re going to weave [prevention, early detection, and treatment] together now over the course of the coming years. [There will be] an escalation in our ability to target other cancer drivers like KRAS and the therapy armamentarium advances [will] continue. But I think what’s particularly exciting is intersecting that trend line with this earlier detection theme, because we just have lots of evidence that deploying the same therapies in earlier disease settings is more effective than later disease settings. Comparing regimens that were first evaluated in metastatic cancer and then deployed in stage II or stage III adjuvant settings, we know that we can cure patients in the stage II and stage III setting, whereas we can’t cure them with the exact same therapy in the metastatic setting. We have the evidence to support the idea that if we deploy these technologies now and leverage them as our guide to iterate on therapies and continue to try to intercept the cancer at an earlier point, we believe that that’s going to profoundly move the needle in the next few years.

I’ll also mention, just around the end of this report came the first positive phase 3 vaccine trial [INTerpath-001; NCT05933577] using an approach that’s been under investigation now for about 10 years: a vaccine that is tailor-made to specific patients based on the mutations found in their cancer that directs the immune system to attack the cancer cells that harbor those mutations. These mutated neoantigen vaccine concepts have been around for a while; we had a positive randomized phase 2 trial in melanoma [KEYNOTE-942; NCT03897881] that led to a phase 3 trial that was just announced as being positive. We haven’t yet seen the data presented at a conference, but we will soon. That’s exciting because that suggests that we have another version of immunotherapy that’s now finally validated and poised to potentially extend across multiple other cancer types as well. So, again, lots of opportunities, lots of reason for optimism, but a lot of work remains.

REFERENCES

1. Primm KM, Blackman E, Zaidi SK, Sengupta R, Sansbury BM. AACR Cancer Progress Report 2026. Clin Cancer Res. 2026;32(19):4246-4249. doi:10.1158/1078-0432.CCR-26-3009

2. O’Sullivan É, Keogh A, Henderson B, Finn SP, Gray SG, Gately K. Treatment strategies for KRAS-mutated non-small-cell lung cancer. Cancers (Basel). 2023;15(6):1635. March 7, 2023. doi:10.3390/cancers15061635

3. Advances in pancreatic cancer research. National Cancer Institute. September 23, 2026. Accessed October 16, 2026. https://tinyurl.com/23c2jcf6