Life Sciences & Biotechnology
Title : | The role of 14-3-3Ï in promoting therapy resistance in colorectal cancer. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. sorab N Dalal, Tata Memorial Centre (Hospital), Maharashtra |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | sdalal@actrec.gov.in |
Equipments : | DNA mini and midi gel apparatuses
Heating Block
Multi channel pipets
Protein mini gel apparatus and accessories |
Details
Executive Summary : | Colorectal cancer (CRC) is a common treatment, with curative surgery being the first line of treatment. stage III and IV tumors are typically treated with adjuvant chemotherapy, such as 5-fluorouracil (5FU) and oxaliplatin. For locally advanced rectal cancer, neo-adjuvant chemo radiotherapy (NACTRT) is the standard of care. Patients who respond to NACTRT undergo surgery, while non-responders receive further chemotherapy. A large number of patients relapse and develop drug-resistant disease. Multiple mechanisms have been postulated to contribute to therapy resistance in CRC, but identifying markers that predict therapy response or targeted therapies that can overcome resistance is not available in clinics. Identifying mechanisms contributing to a decrease in therapy response will improve patient outcomes. 14-3-3Ï expression is decreased in various epithelial tumor types, particularly breast tumors. Loss of 14-3-3Ï leads to immortalization in keratinocytes and growth of breast tumors. Previous research has shown that loss of 14-3-3Ï in HCT116 cells leads to premature cell death upon double strand breaks in the colorectal cancer cell line HCT116. This leads to the induction of the Epithelial Mesenchymal Transition (EMT), which is associated with therapy resistance in multiple tumor types, including colon cancer cell lines and tissues. Preliminary data show that loss of 14-3-3Ï leads to a decrease in resistance to 5FU, an increase in nuclear localization of YY1, and a decrease in the expression of genes required for the Unfolded Protein Response (UPR). This hypothesis will be tested in this proposal, potentially identifying novel targets for sensitizing therapy-resistant tumors to chemotherapy. |
Co-PI: | Dr. sanjay Gupta, Tata Memorial Centre Advanced Centre For Treatment, Research And Education In Cancer, New Mumbai, Maharashtra-410210 |
Total Budget (INR): | 74,60,400 |
Organizations involved