Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.
Abstract
Despite the ongoing advances in interventional strategies (surgery, chemotherapy, radiotherapy, and immunotherapy) for managing pancreatic ductal adenocarcinoma (PDAC), the development of therapy refractory phenotypes remains a significant challenge. Resistance to various therapeutic modalities in PDAC emanates from a combination of inherent and acquired factors and is attributable to cancer cell-intrinsic and -extrinsic mechanisms. The critical determinants of therapy resistance include oncogenic signaling and epigenetic modifications that drive cancer cell stemness and metabolic adaptations, CAF-mediated stromagenesis that results in ECM deposition altered mechanotransduction, and secretome and immune evasion. We reviewed the current understanding of these multifaceted mechanisms operating in the PDAC microenvironment, influencing the response to chemotherapy, radiotherapy, and immunotherapy regimens. We then describe how the lessons learned from these studies can guide us to discover novel therapeutic regimens to prevent, delay, or revert resistance and achieve durable clinical responses.
EDRN PI Authors
Medline Author List
- Batra SK
- Ganguly K
- Ganti AK
- Jain M
- Khan I
- Kumar S
- Ponnusamy MP
- Rauth S
- Shah A
- Sheree SS
PubMed ID
Sources
- Cancer Data Expo