Significance

The increase in the prevalence of cancer in different parts of the world is due to the presence of drug resistance mechanisms and escape pathways in tumor cells. Despite the development of biological and chemotherapeutic agents to combat drug resistance in cancer cells, there are certain barriers to their successful application.

In recent international collaboration, researchers led by Professor Tayyaba Hasan at Massachusetts General Hospital, Harvard Medical School investigated the effect of photodynamic priming on the potency and sustained anti-tumor activity of nanoliposomal irinotecan. They demonstrated that photodynamic priming results in the simultaneous increase in the efficacy and sustained anti-tumor activity of nanoliposomal irinotecan and enhance survival outcomes. The research work is now published in Journal, Cancer Research.

The authors observed that the presence of photodynamic priming resulted in an increase in the permeability and accumulation of nanoliposomal irinotecan in tumor blood vessels and tissue while the absence of photodynamic priming resulted in the reduced accumulation and permeability of nanoliposomal irinotecan in tumors. The authors also observed that the intravenous administration of nanoliposomal irinotecan resulted in a 0.35 %ID/g increase in tumoral irinotecan after 24 hours while the combination of photodynamic priming and nanoliposomal irinotecan treatment resulted in an impressive 11-fold increase (3.5%ID/g) in tumoral irinotecan, even after 72 hours.

The study also shows that nanoliposomal irinotecan significantly reduced the growth of tumor cells by 89%, while a combination of photodynamic priming and nanoliposomal irinotecan reduced the growth of tumor cells by 96%. Photodynamic priming was agnostic to the cell type in its killing ability: both cancer stem cells and non-stem cancer cells were killed. Nanoliposomal irinotecan, is an approved treatment option for pancreatic cancer in the metastatic setting. The cellular-molecular effects observed with photodynamic priming resulted in delayed regrowth of tumors in animals, after the termination of treatment, only when chemotherapy with nanoliposomal irinotecan was preceded by photodynamic priming when tested in pancreatic cancer models. Moreover, the proposed strategy of using a combination of photodynamic priming and nanoliposomal irinotecan significantly reduced the burden of metastasis, prolonged overall survival and demonstrated cure in 25% of the pancreatic cancer –bearing animals.

With regard to safety of photodynamic priming strategy, their findings indicate that the use of photodynamic priming did not increase the systemic toxicity.

The study provided initial successful evidence of the efficacy of photodynamic priming in the reduction of the risks of tumor regrowth, drug resistance and progression, and extension of survival outcomes in preclinical cancer models. Thus, their findings serve as a basis for the development of improved photodynamic priming-based approaches that enhances drug accessibility and reduces molecular selective pressures induced by long-term cancer treatments.

Reference

Huang, H.C., Rizvi, I., Liu, J., Anbil, S., Kalra, A., Lee, H., Baglo, Y.M., Paz, N., Hayden, D., Pereira, S., Pogue, B.W., Fitzgerald, J., and Hasan, T. (2017). Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves Drug Delivery, Cancer Research , 78 (2), 558-571.