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Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment
Open accessAbstract
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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“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).”
From Cross-talk between HIF and PD-1/PD-L1 pathways in carcinogenesis and therapy (2022) · cites this paper as [5]
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Metadata
- 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
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2022-01-21
- Volume
- 14
- Issue
- 3
- Pages
- 539
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC8833523
- 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
- gold
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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