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The estrogen pathway as a modulator of response to immunotherapy

Maria A Velez1, Timothy F Burns2,3,4, Laura P Stabile2,4

  • 1Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Immunotherapy
|July 31, 2019
PubMed

Insights

Estrogen signaling in non-small cell lung cancer (NSCLC) may impact treatment outcomes and sex-based responses to immune checkpoint inhibitors (ICIs). Targeting estrogen pathways could offer new therapeutic strategies for NSCLC patients.

Area of Science:

  • Oncology
  • Immunology
  • Endocrinology

Background:

  • Lung cancer remains a leading cause of cancer mortality globally, with limited treatment efficacy for many patients.
  • Immune checkpoint inhibitors (ICIs) show promise but benefit only a subset of non-small cell lung cancer (NSCLC) patients.
  • The estrogen signaling pathway is increasingly implicated in NSCLC development and treatment response.

Purpose of the Study:

  • To review current data on the estrogen pathway in NSCLC.
  • To explore the role of estrogen signaling in sex-based differences in response to ICIs.
  • To evaluate the potential of antiestrogen therapy combined with ICIs for NSCLC treatment.

Main Methods:

  • Review of epidemiologic data.
  • Analysis of preclinical studies.
  • Evaluation of clinical trial outcomes.

Main Results:

  • Evidence suggests estrogen signaling influences NSCLC progression.
  • The estrogen pathway may mediate differential responses to ICIs between sexes.
  • Antiestrogen therapies are being investigated for synergistic effects with ICIs.

Conclusions:

  • The estrogen pathway represents a potential therapeutic target in NSCLC.
  • Understanding estrogen's role could personalize ICI therapy and improve outcomes.
  • Combination therapy with antiestrogens and ICIs warrants further clinical investigation.
Keywords:
antiestrogen therapycheckpoint inhibitorsestrogen pathwaynon-small-cell lung cancersex differencestumor microenvironment

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