4.6 Review

Targeted Therapies for Pancreatic Cancer: Overview of Current Treatments and New Opportunities for Personalized Oncology

Journal

CANCERS
Volume 13, Issue 4, Pages -

Publisher

MDPI
DOI: 10.3390/cancers13040799

Keywords

pancreatic ductal adenocarcinoma; therapies; DNA repair; tumor microenvironment; epigenetic alterations; key mutations; autophagy; immunotherapy

Categories

Funding

  1. Swiss National Science Foundation (SNSF) [PP00P3_194810]
  2. Swiss National Science Foundation (SNF) [PP00P3_194810] Funding Source: Swiss National Science Foundation (SNF)

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The lack of early diagnosis, absence of suitable biomarkers, and resistance to available therapeutic options make pancreatic cancer one of the deadliest cancer types, necessitating the development of new therapeutic approaches. By considering the genetic and molecular profile of pancreatic tumors, potent and specific antitumor compounds can be developed to change this recalcitrant cancer type into a manageable one.
Simple Summary The lack of early diagnosis and the absence of suitable biomarkers coupled with resistance to available therapeutic options render pancreatic cancer one of the deadliest cancer types. Therefore, new therapeutic approaches are needed to be developed, taking into account the genetic and molecular profile of pancreatic tumors. Here, we critically review past and current efforts that have resulted in the development of potent and specific antitumor compounds that, if employed in the appropriate combination therapy, may change this recalcitrant cancer type into a manageable one. Cytotoxic chemotherapy remains the only treatment option for most pancreatic ductal adenocarcinoma patients. Currently, the median overall survival of patients with advanced disease rarely exceeds 1 year. The complex network of pancreatic cancer composed of immune cells, endothelial cells, and cancer-associated fibroblasts confers intratumoral and intertumoral heterogeneity with distinct proliferative and metastatic propensity. This heterogeneity can explain why tumors do not behave uniformly and are able to escape therapy. The advance in technology of whole-genome sequencing has now provided the possibility of identifying every somatic mutation, copy-number change, and structural variant in a given cancer, giving rise to personalized targeted therapies. In this review, we provide an overview of the current and emerging treatment strategies in pancreatic cancer. By highlighting new paradigms in pancreatic ductal adenocarcinoma treatment, we hope to stimulate new thoughts for clinical trials aimed at improving patient outcomes.

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