Expression of anti-apoptotic proteins in pancreatic cancers: A potential barrier to photodynamic killing
Mentor: Tayyaba Hasan, PhD (Massachusetts General Hospital)
Pancreatic cancer is rarely symptomatic until it has metastasized to other parts of the body. In 2019, it is predicted that about 56,770 people will be diagnosed with pancreatic cancer and about 45,750 will die from it. This is because most pancreatic cancers develop resistance to chemotherapeutic drugs, leaving current treatments like chemotherapy and combination chemo-radiation therapy ineffective. The resistance to existing therapies and the associated low survival rates in pancreatic cancers highlights the need for more effective therapies that can overcome the resistant properties of these cancers. Photodynamic therapy (PDT) provides an alternate treatment modality for chemo-resistant tumors. It involves the irradiation of tumor-localized photosensitizers for the generation of reactive molecular species (RMS) and induction of apoptosis/necrosis. In this study, we use four model pancreatic cancer cell lines: KPC and Pan 02 (mouse pancreatic cancer cell lines); MiaPaCa2 and AsPC-1 (human pancreatic cancer cell lines) to explore the therapeutic effects of PDT. These cell lines represent pancreatic cancers with or without Kras mutation (mutation in Kras leads to treatment resistant tumors) and differential Kras expression levels. In our preliminary studies, we observed variations in photosensitizer uptake efficiency and ROS generation in these cell lines, resulting in differences in PDT efficiency. Further studies will be aimed at comparing the levels of anti-apoptotic proteins (survivin, Bcl2, etc) in these cells and the effect of PDT on their expression. The overarching goal of this study is to further understand the mechanism of resistance in pancreatic cancers in an attempt to develop efficient therapeutic modalities.
a) Photodynamic therapy (PDT): Photosensitizers, in different formulations (free BPD or liposomal formulation), are added to target tissues and irradiated, resulting in apoptosis/necrosis. b) Tumor cells have different survival mechanisms when exposed to therapeutic agents. In the present study, we are exploring the expression of anti-apoptotic proteins as a possible survival pathway, post-PDT. Source: