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Mitogen-Activated Protein Kinase and Nuclear Hormone Receptor Crosstalk in Cancer Immunotherapy

Elke Burgermeister1

  • 1Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.

International Journal of Molecular Sciences
|September 9, 2023
PubMed

Insights

Mitogen-activated protein kinase (MAPK) pathways regulate nuclear hormone receptors (NHRSFs), impacting cancer and immunity. Targeting these pathways offers potential for novel cancer immunotherapies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • Mitogen-activated protein kinase (MAPK) pathways (ERK1/2, p38, JNK/SAPK) are key regulators of the nuclear hormone receptor superfamily (NHRSF).
  • NHRSFs, like the estrogen receptor, play critical roles in cancer, particularly breast cancer.
  • Cross-talk between MAPK pathways and NHRSFs influences gene transcription involved in cell functions and immune responses.

Purpose of the Study:

  • To review the literature on NHRSF subclasses in human tumors (solid and leukemias).
  • To explore the functional roles of NHRSFs in the tumor microenvironment, including immune cells.
  • To discuss the therapeutic potential of targeting MAPK and NHRSF pathways, especially in cancer immunotherapy.

Main Methods:

  • Literature review of existing studies on NHRSF expression and function in various human cancers.
  • Analysis of the interplay between MAPK signaling and NHRSFs in both cancer cells and immune cells.
  • Examination of combined therapeutic strategies involving NHRSFs and immune checkpoint inhibitors (e.g., PD1).

Main Results:

  • NHRSFs are expressed across diverse human tumors, including solid cancers and leukemias.
  • The interaction between MAPK and NHRSF pathways affects critical cellular processes and immune modulation within the tumor microenvironment.
  • NHRSFs demonstrate functional roles in immune cells, influencing the adaptive and innate immune system's response to tumors.

Conclusions:

  • The drugability of both MAPK and NHRSF pathways presents significant opportunities for developing novel cancer therapies.
  • Combination therapies targeting NHRSFs with existing immunotherapeutics, such as PD1 inhibitors, show promise for enhancing cancer immunotherapy.
  • Further research into the molecular crosstalk between MAPK, NHRSFs, and the immune system is crucial for advancing precision oncology.
Keywords:
MAPKcancerhormoneimmunotherapykinasenuclear receptor

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