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Updated: Oct 9, 2025

Evaluating Autophagy Levels in Two Different Pancreatic Cell Models Using LC3 Immunofluorescence
08:07

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Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma

Alexander G Raufi1,2,3,4, Nicholas R Liguori1,5, Lindsey Carlsen1,3,4,6

  • 1Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States.

Frontiers in Pharmacology
|December 17, 2021
PubMed

Insights

Autophagy inhibition shows promise for pancreatic cancer therapy. Combining MAPK pathway inhibitors with autophagy inhibitors, or using agents like ONC212, may offer new treatment strategies for pancreatic ductal adenocarcinoma (PDAC).

Area of Science:

  • Oncology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with limited treatment options.
  • Autophagy, a cellular recycling process, is implicated in PDAC progression and survival.
  • Previous clinical trials of autophagy inhibitors in PDAC have yielded disappointing results.

Purpose of the Study:

  • To explore the role of autophagy in pancreatic cancer.
  • To review novel therapeutic strategies targeting autophagy in PDAC.
  • To discuss the interplay between the MAPK pathway and autophagy inhibition.

Main Methods:

  • Review of preclinical and clinical data on autophagy modulators in PDAC.
  • Discussion of autophagy's role in PDAC tumorigenesis, metabolism, and immune response.
  • Examination of emerging therapeutic agents and combinations.

Main Results:

  • Autophagy plays a complex role in PDAC, influencing carcinogenesis, metastasis, and survival.
  • Early clinical trials with autophagy inhibitors alone or with chemotherapy were not successful.
  • Synergy observed between MAPK pathway inhibitors and autophagy inhibitors in preclinical models.
  • Novel agents like ONC212 show preclinical efficacy in pancreatic cancer via autophagy inhibition.

Conclusions:

  • Targeting autophagy presents a potential therapeutic avenue for PDAC.
  • Combination therapies, particularly involving MAPK pathway modulation, warrant further investigation.
  • Novel agents and strategies targeting autophagy may improve outcomes for pancreatic cancer patients.
Keywords:
Atg5LC3MEK inhibitorsONC212autophagybeclin 1chloroquinepancreatic cancer

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