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Developing effective combination therapy for pancreatic cancer: An overview.

Aubrey L Miller1, Patrick L Garcia1, Karina J Yoon1

  • 1Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham AL, 35294 USA.

Pharmacological Research
|March 6, 2020
PubMed
Summary

Pancreatic cancer has a poor prognosis, with gemcitabine offering limited efficacy. Novel combination therapies targeting BET proteins and DNA repair pathways show promise for improving outcomes in this deadly disease.

Keywords:
AZD6738 (PubChem CID: 54761306)BET bromodomain inhibitorsBevacizumab (PubChem SID: 46504473)Cetuximab (PubChem SID: 46507042)Erlotinib (PubChem CID: 176870)GemcitabineGemcitabine (PubChem CID: 60750)JQ1 (PubChem CID: 49871818)MK-8776 (PubChem CID: 46239015)Nivolumab (PubChem SID: 178103907)Olaparib (PubChem CID: 23725625)PARP inhibitorsPancreatic cancerVorinostat (PubChem CID: 5311)

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Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Pancreatic cancer exhibits a dismal five-year survival rate below 10%.
  • Drug-resistant, metastatic disease is the primary cause of mortality.
  • Gemcitabine, a standard chemotherapy, is not curative as a single agent.

Purpose of the Study:

  • To review preclinical and clinical strategies for pancreatic cancer therapy.
  • To identify agents targeting common molecular features of pancreatic tumors.
  • To explore mechanism-based combination therapies for improved treatment efficacy.

Main Methods:

  • Review of preclinical studies on novel therapeutic agents.
  • Analysis of clinical trial data for combination therapies.
  • Focus on agents targeting BET proteins and DNA repair mechanisms.

Main Results:

  • BET bromodomain inhibitors show potential in targeting transcription.
  • PARP inhibitors demonstrate efficacy in addressing DNA repair.
  • Combination approaches are emerging as promising therapeutic strategies.

Conclusions:

  • Developing effective therapies for pancreatic cancer remains a critical unmet need.
  • Targeting molecular pathways with novel agents, particularly in combination, offers hope.
  • BET bromodomain and PARP inhibitors represent promising avenues for future pancreatic cancer treatment.