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New Insights as to Why Progesterone Receptor Modulators, such as Mifepristone, Seem to Be More Effective in Treating

Jerome H Check1,2, Diane Check2

  • 1Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology & Infertility, Cooper Medical School of Rowan University, Camden, NJ, U.S.A.; laurie@ccivf.com.

Anticancer Research
|December 1, 2021
PubMed

Insights

Mifepristone improves cancer patient outcomes by targeting progesterone-induced blocking factor (PIBF). However, its effectiveness may be limited in cancers with nuclear progesterone receptors (nPR), potentially due to interactions with progesterone receptor membrane component-1 (PGRMC-1).

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Mifepristone shows promise in advanced cancer, improving patient quality and length of life.
  • Progesterone-induced blocking factor (PIBF) aids tumor invasion, proliferation, and immune suppression.
  • Benefits are notable in cancers lacking the classical nuclear progesterone receptor (nPR).

Purpose of the Study:

  • To investigate the mechanism of mifepristone in advanced cancers.
  • To explore the role of progesterone receptors (PRs) in mifepristone efficacy.
  • To understand the interplay between PIBF, nPR, and PGRMC-1 in cancer progression.

Main Methods:

  • Analysis of mifepristone treatment outcomes in advanced cancer patients.
  • Investigation of PIBF and PR expression in tumor tissues.
  • Exploration of the interaction between mifepristone, nPR, and PGRMC-1.

Main Results:

  • Mifepristone treatment improved survival and quality of life in patients with limited options.
  • PIBF is a key target, implicated in tumor spread and immune evasion.
  • Efficacy appears higher in cancers without nPR; nPR presence may correlate with better prognosis.
  • Membrane PRs (mPRs) are linked to PIBF secretion.
  • Mifepristone might not block PGRMC-1, a protein promoting tumor proliferation.
  • nPR may inhibit PGRMC-1 production, suggesting a complex regulatory role.

Conclusions:

  • Mifepristone's anti-cancer effects are mediated by PIBF suppression.
  • The presence or absence of nPR influences mifepristone's efficacy, possibly via PGRMC-1 regulation.
  • Further research is needed to elucidate the nPR/PGRMC-1 pathway for optimizing mifepristone therapy.
Keywords:
Progesterone induced blocking factorcellular immunityimmunomodulatory proteinsprogesterone receptor membrane receptor component-1reviewtumor microenvironment

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