Novel systemic treatment approaches for metastatic pancreatic cancer

Expert Opin Investig Drugs. 2022 Mar;31(3):249-262. doi: 10.1080/13543784.2022.2037552. Epub 2022 Feb 10.

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year overall survival rate of 10%, emphasizing the need for more effective therapies, especially in metastatic disease. The immunosuppressive tumor microenvironment, poor vascularization, and dense tumor stroma typical for PDAC are hurdles that need to be overcome by novel drugs. Investigations are moving toward more targeted treatments including immunotherapy and cell-based approaches.

Areas covered: This article reviews emerging drugs in clinical development for metastatic PDAC, focusing on cellular therapies and novel treatments targeting metabolism, tumor stroma, oncogenic pathways and immunosuppression. With immunotherapy and CAR T-cell therapy on the rise in hematological malignancies, the transfer to solid tumors remains intriguing. Multiple exciting clinical trials investigating innovative therapeutic strategies for PDAC are currently ongoing and reviewed herein. ClinicalTrials.gov, conference abstracts and PubMed were searched in August 2021 and assessed for information on ongoing and published clinical studies.

Expert opinion: With many challenges to overcome, the optimal therapy for patients with metastatic PDAC is likely to consist of a combination of different agents. We are slowly moving from entity-dependent approaches to ones more focused on molecular and pathological features. Increasingly personalized treatment plans tailored to each patient may be the future of PDAC therapy.

Keywords: Pancreatic cancer; cellular therapy; immunotherapy; metastatic; novel drugs; targeted therapy.

Publication types

  • Review

MeSH terms

  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Carcinoma, Pancreatic Ductal* / pathology
  • Humans
  • Immunotherapy
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / pathology
  • Tumor Microenvironment