TY - JOUR
T1 - Treatment resistance in pancreatic and biliary tract cancer
T2 - molecular and clinical pharmacology perspectives
AU - Toledo, Belén
AU - Deiana, Chiara
AU - Scianò, Fabio
AU - Brandi, Giovanni
AU - Marchal, Juan Antonio
AU - Perán, Macarena
AU - Giovannetti, Elisa
N1 - Publisher Copyright: © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2024
Y1 - 2024
N2 - Introduction: Treatment resistance poses a significant obstacle in oncology, especially in biliary tract cancer (BTC) and pancreatic cancer (PC). Current therapeutic options include chemotherapy, targeted therapy, and immunotherapy. Resistance to these treatments may arise due to diverse molecular mechanisms, such as genetic and epigenetic modifications, altered drug metabolism and efflux, and changes in the tumor microenvironment. Identifying and overcoming these mechanisms is a major focus of research: strategies being explored include combination therapies, modulation of the tumor microenvironment, and personalized approaches. Areas covered: We provide a current overview and discussion of the most relevant mechanisms of resistance to chemotherapy, target therapy, and immunotherapy in both BTC and PC. Furthermore, we compare the different strategies that are being implemented to overcome these obstacles. Expert opinion: So far there is no unified theory on drug resistance and progress is limited. To overcome this issue, individualized patient approaches, possibly through liquid biopsies or single-cell transcriptome studies, are suggested, along with the potential use of artificial intelligence, to guide effective treatment strategies. Furthermore, we provide insights into what we consider the most promising areas of research, and we speculate on the future of managing treatment resistance to improve patient outcomes.
AB - Introduction: Treatment resistance poses a significant obstacle in oncology, especially in biliary tract cancer (BTC) and pancreatic cancer (PC). Current therapeutic options include chemotherapy, targeted therapy, and immunotherapy. Resistance to these treatments may arise due to diverse molecular mechanisms, such as genetic and epigenetic modifications, altered drug metabolism and efflux, and changes in the tumor microenvironment. Identifying and overcoming these mechanisms is a major focus of research: strategies being explored include combination therapies, modulation of the tumor microenvironment, and personalized approaches. Areas covered: We provide a current overview and discussion of the most relevant mechanisms of resistance to chemotherapy, target therapy, and immunotherapy in both BTC and PC. Furthermore, we compare the different strategies that are being implemented to overcome these obstacles. Expert opinion: So far there is no unified theory on drug resistance and progress is limited. To overcome this issue, individualized patient approaches, possibly through liquid biopsies or single-cell transcriptome studies, are suggested, along with the potential use of artificial intelligence, to guide effective treatment strategies. Furthermore, we provide insights into what we consider the most promising areas of research, and we speculate on the future of managing treatment resistance to improve patient outcomes.
KW - Biliary tract cancer
KW - chemoresistance
KW - chemotherapy
KW - immunoresistance
KW - immunotherapy
KW - pancreatic cancer
KW - resistance mechanisms
KW - target therapy
UR - http://www.scopus.com/inward/record.url?scp=85188464415&partnerID=8YFLogxK
U2 - 10.1080/17512433.2024.2319340
DO - 10.1080/17512433.2024.2319340
M3 - Review article
C2 - 38413373
SN - 1751-2433
VL - 17
SP - 323
EP - 347
JO - Expert Review of Clinical Pharmacology
JF - Expert Review of Clinical Pharmacology
IS - 4
ER -