Cited by 32Cancer, Hypoxia, and MetabolismHepatocellular Carcinoma Treatment and PrognosisAngiogenesis and VEGF in Cancer

Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment

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Lappano, Rosamaria, Todd, Lauren A., Stanic, Mia, Cai, Qi, Maggiolini, Marcello, Marincola, Francesco, Pietrobon, Violena·2022·Cancers

Abstract

Hormones and growth factors (GFs) are signaling molecules implicated in the regulation of a variety of cellular processes. They play important roles in both healthy and tumor cells, where they function by binding to specific receptors on target cells and activating downstream signaling cascades. The stages of tumor progression are influenced by hormones and GF signaling. Hypoxia, a hallmark of cancer progression, contributes to tumor plasticity and heterogeneity. Most solid tumors contain a hypoxic core due to rapid cellular proliferation that outgrows the blood supply. In these circumstances, hypoxia-inducible factors (HIFs) play a central role in the adaptation of tumor cells to their new environment, dramatically reshaping their transcriptional profile. HIF signaling is modulated by a variety of factors including hormones and GFs, which activate signaling pathways that enhance tumor growth and metastatic potential and impair responses to therapy. In this review, we summarize the role of hormones and GFs during cancer onset and progression with a particular focus on hypoxia and the interplay with HIF proteins. We also discuss how hypoxia influences the efficacy of cancer immunotherapy, considering that a hypoxic environment may act as a determinant of the immune-excluded phenotype and a major hindrance to the success of adoptive cell therapies.

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Crossref · 10.3390/cancers14030539

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  • Hypoxia impacts the efficiency of cancer immunotherapy by contributing to the immune-eliminated phenotype.

    “For instance, hypoxia impacts the efficiency of cancer immunotherapy by contributing to the immune-eliminated phenotype, which is a key barrier to the therapeutic effect of adoptive cell therapy (5).”

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  1. [9]Stone W.L. Leavitt L. Varacallo M. Physiology, Growth Factor StatPearls Publishing Treasure Island, FL, USA 2017 28723053

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Authors
Lappano, R., Todd, L. A., Stanic, M., Cai, Q., Maggiolini, M., Marincola, F., & Pietrobon, V.
Affiliations
  • University of Calabria (IT)
  • University of Waterloo (CA)
  • Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
  • Kite Pharma (United States) (US)
Corresponding author
  • Lappano, Rosamaria
  • Pietrobon, Violena
Venue
Cancers
Publisher
MDPI AG
Published
2022-01-21
Volume
14
Issue
3
Pages
539
ISSN
2072-6694 (ISSN-L)
OpenAlex
W4207059954
Cited by
32
References
460
Citations by year
2026: 8 · 2025: 11 · 2024: 5 · 2023: 5 · 2022: 3
FWCI
0.72
Type
journal article
Language
en
Open access
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • TSpace (University of Toronto) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
Funders
Italian Association for Cancer Research (IG 21322)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
tumor microenvironment, hormones, growth factors, hypoxia, hypoxia-inducible factor, HIF signaling, tumor progression, tumor heterogeneity, metastasis, cancer immunotherapy, immune-excluded phenotype, adoptive immunotherapy, treatment resistance

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