Research Projects

As per the worldwide cancer statistics in men, the second most cause of death due to malignancy is prostate cancer (PCa). It was predicted that in 2021, PCa would account for 26% of new cancer cases of non-cutaneous origin. In PCa, metastasis issue can be addressed by androgen deprivation therapy initially but over time patient may develop castrate-resistant PCa (CRPC) which have no curative treatment to date. With the advancement of new drugs against PCa the survival rate of the metastatic CRPC patients still remain low, i.e. around five years. The great challenge of dealing with PCa is that it can recur many years after the disease was assumed to be healed by chemotherapy, radiation or surgery. It is very common practice of using chemotherapeutic agents to handle wide variety of malignant cancers. While effective, some chemotherapeutic agents pose significant toxicity and patients gradually develop resistance against the drugs during the treatment period, as a result tumor relapse takes place. It is well established that inflammation is associated with the progression of tumorigenesis and carcinogenesis. Inflammasomes consist of certain multi-protein complexes which produces numerous inflammatory reactions inside the cells that is perilous for maintaining homeostasis. NOD like receptor protein 3 (NLRP3) binds and activates caspase-1 that triggers the maturation of inflammatory cytokines including IL-1β and IL-18, which are responsible for initiation of inflammatory response. Inflammasome components and pathways may provide novel targets to treat inflammation and associated cancer. As a result of chemotherapeutic treatment, cancer cells secret many factors through the activation of the inflammasome, where IL-1β and IL-18 play important role. Because of their pro-inflammatory nature, they share certain pro-proliferating signalling responsible for cancer progression. So, it would be important to examine the signalling pathways involved during chemotherapy resistant prostate cancer progression in connection with inflammasome activation. Objective 1: To find out different factors involved in inflammasome formation in Prostate cancer. 2: To find out different factors involved in inflammasome formation in Prostate cancer after chemotherapy. 3: To find out the factors responsible in inflammosome formation in chemo-resistant PCa cells. 4: To determine the role of identified inflammosome molecules in chemotherapy resistant Prostate cancer progression. 5: Targeting of inflammosome molecules using standard chemotherapeutics for checking synergistic effects on resistant PCa cells. Significance: Till date no drugs are available for treatment of chemo resistant PCa. The number of PCa cases have increased tremendously in India in the last decade warranting newer intervention strategies for the disease. Synergistic targeting the inflammatory module alongside chemotherapy drugs might provide novel intervention strategies for resistant PCa.