Repurposing quinacrine for treatment-refractory cancer

Derek B. Oien, Christopher L. Pathoulas, Upasana Ray, Prabhu Thirusangu, Eleftheria Kalogera, Viji Shridhar

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations

Abstract

Quinacrine, also known as mepacrine, has originally been used as an antimalarial drug for close to a century, but was recently rediscovered as an anticancer agent. The mechanisms of anticancer effects of quinacrine are not well understood. The anticancer potential of quinacrine was discovered in a screen for small molecule activators of p53, and was specifically shown to inhibit NFκB suppression of p53. However, quinacrine can cause cell death in cells that lack p53 or have p53 mutations, which is a common occurrence in many malignant tumors including high grade serous ovarian cancer. Recent reports suggest quinacrine may inhibit cancer cell growth through multiple mechanisms including regulating autophagy, FACT (facilitates chromatin transcription) chromatin trapping, and the DNA repair process. Additional reports also suggest quinacrine is effective against chemoresistant gynecologic cancer. In this review, we discuss anticancer effects of quinacrine and potential mechanisms of action with a specific focus on gynecologic and breast cancer where treatment-refractory tumors are associated with increased mortality rates. Repurposing quinacrine as an anticancer agent appears to be a promising strategy based on its ability to target multiple pathways, its selectivity against cancer cells, and the synergistic cytotoxicity when combined with other anticancer agents with limited side effects and good tolerability profile.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalSeminars in Cancer Biology
Volume68
DOIs
StatePublished - Jan 2021

Keywords

  • Breast cancer
  • Drug repurposing
  • Endometrial cancer
  • Ovarian cancer
  • Quinacrine

ASJC Scopus subject areas

  • Cancer Research

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