Research

Life Sciences & Biotechnology

Title :

Studies on inhibition of SHP2/PTPN11 pathway to overcome chemo-resistance in PDAC using targeted combination therapy

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Kiran Kumar Tejavath, Central University Of Rajasthan

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

Around the world mortality rates of pancreatic cancer (PC) according to GLOBOCAN 2020 is 93.99% (4,66,003 out of 4,95,773) and in India is 96.13% (12,153 out of 12,642) most of which is pancreatic ductal adenocarcinoma (PDAC). Developing countries like India, have changing lifestyle and eating habits which acts as one of the inducements for raising PDAC cases. Present regimen against PDAC includes chemotherapy, radiotherapy, immunotherapy and surgery. From among different FDA approved drugs for treatment of PDAC some are Abraxane, 5-Fluorouracil, Paclitaxel, Erlotinib, etc; and gold standard drug gemcitabine. But often these drugs have issues like resistance, off target toxicity, lower uptake, and metabolism related complications which lead to requirement of higher and repetitive drug doses. To overcome these hindrances solutions like combination therapy and treatment by loading drugs into targeted nanoformulations is gaining importance. Considering the above facts and ongoing research against PDAC, the proposed project visions for synthesis of targeted liposomes that will be functionalized with PR_b peptide and could efficiently load SHP2 inhibitor and gemcitabine for combination therapy against PDAC. The PR_b peptide functionalization will increase nanoformulations accumulation at the tumor site minimizing the side-effects on normal cells. Initially the SHP2 inhibitor will be checked for its efficacy on PDAC both alone as well as in combination with gemcitabine. Then the combination index at which these 2 drugs act synergistically will be determined followed by loading them into the liposomes. The liposomes at every step of synthesis will be subjected to characterization methods and on obtaining required liposomes they will be tested for their efficiency against PDAC cells in 2D and 3D models along with normal cells to confirm the reduced toxicity of drugs alone. Hence, this project will bring out better therapy option in the fight against PDAC to ultimately help increase hopes of survival.

Total Budget (INR):

30,03,000

Organizations involved