"In the case of sarcomas treated with the current standard of care, doxorubicin, tumors may be initially responsive in their primary location, but become unresponsive after metastasis to the lungs, which eventually becomes the most likely cause of patients' death."
At the 2020 American Association of Cancer Research (AACR) Virtual Annual Meeting, a presentation of annamycin showed there was a high uptake and retention of the anthracycline antibiotic in the subjects’ lungs, which resulted in consistently high in vivo activity in the study subjects with a wide range of lung-localized tumors.1
The study established there were high levels of annamycin in lung tissue of the subjects in biodistribution experiments. The annamycin levels in subjects’ lungs were 6 times greater than doxorubicin and, on a cellular level, immunofluorescence and fluorescence activated cell sorting analysis showed significantly higher uptake of annamycin. This drug exhibited high antitumor activity ranging from the inhibition of tumor progression to complete tumor eradication in bioluminescent imaging in models of lung-localized cancers. In all the tested models, the delay in tumor growth or tumor regression led to a significant improvement in survival.2
The sarcoma lung metastasis model showed that the subjects had a median survival of 87.5 days on annamycin versus 21 days with saline. The survival ratio was 4.17 and 1, respectively, with a P value of <.0001.
Investigators wrote in the poster presentation that the high cytotoxic potency of the drug against multidrug related cancer cells was partly due to annamycin’s ability to overcome ATP-binding cassette transporter-mediated efflux and achieve a high intracellular uptake compared with doxorubicin (Adriamycin). There was an increased concentration of annamycin in the lung when put in contrast with doxorubicin, which led to efficacy in vivo in lung-localized tumor models.
Overall, the study supported the hypothesis of lungs being the sanctuary site for cancer cells and it showed that effective targeting of metastases in the lungs is possible through chemical modification of clinically used drugs which are currently ineffective. This is especially true when the drug is used in combination with appropriate drug delivery. The investigators also noted these data indicate this approach can lead to the identification and elimination of cancer sanctuary sites other than the lungs and the creation of more effective treatments for patients.
"We are very encouraged by this data, as we believe it further demonstrates Annamycin's anti-cancer activity against tumors that evade therapies that may be initially effective in their primary location of origin but are protected by metastasis to sanctuary organs,” Walter Klemp, chairman and chief executive officer of Moleculin Biotech Inc., said in a press release. “In the case of sarcomas treated with the current standard of care, doxorubicin, tumors may be initially responsive in their primary location, but become unresponsive after metastasis to the lungs, which eventually becomes the most likely cause of patients' death."1
"This research also sheds light on why doxorubicin, the current standard of care for many types of cancer, is not effective against lung-localized cancer,” he continued. “Subsequently, we believe that annamycin's ability in animal models to effectively accumulate in the lungs without noticeable [adverse] effects offers unique therapeutic opportunities that should be explored for the benefit of cancer patients with lung-localized tumors."
Moleculin, a pharmaceutical company which looks at clinical stage drugs which are candidates for targeting highly resistant tumors and viruses, supported the investigation of this drug through a grant to the University of Texas MD Anderson Cancer Center in Houston. Their approach is to create therapies capable of reaching tumors within organs, unlike the existing anticancer drugs, which can’t accumulate in therapeutic concentrations.
1. Moleculin Announces Preclinical Data Confirms Efficacy of Annamycin in Lung Metastases [press release]. PRNewswire. Published June 25, 2020. Accessed June 25, 2020. https://prn.to/3dtq54g
2. Zielinski R, Grela K, Zuniga RC, et al. Targeting sanctuary sites of cancer: Novel approaches to treatment of lung localized tumors. Poster presented at: 2020 AACR Annual Meeting; June 22-24, 2020.