Page 188 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Research on hypoxia and ECM in cancer

Table 5. Top 20 keywords by frequency and anti-tumor immunity. This combination therapy
effectively reduced ECM components, enhanced vessel
Rank Keyword Frequency diameter, and pericyte coverage, and decreased tumor
1 Hypoxia 168 size in TNBC mouse models. Tranilast also enhanced
2 Extracellular matrix 136 tumor immune microenvironment normalization,
3 Microenvironment 113 increased T-cell infiltration, and improved the efficacy of
4 Breast cancer 76 immune checkpoint inhibitors anti-PD-1/anti-CTLA-4,
5 Metastasis 72 offering a promising strategy for enhancing cancer
50
6 Angiogenesis 58 therapy. Photodynamic therapy (PDT) is a relatively
new alternative technique for TNBC treatment that
7 Invasion 49 combines chemotherapy and nanomaterials to enhance
8 Epithelial-mesenchymal transition 47 its therapeutic effect by relieving tumor hypoxia. 51-53 Xiang
9 Stem-cell 31 et al. uncovered that intratumoral hypoxia in breast
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10 Cancer-associated fibroblast 29 cancer fosters the enrichment of breast cancer stem cells
11 Proliferation 26 (BCSCs) through HIF-1-mediated upregulation, as well as
12 Hypoxia-inducible factor 25 TAZ activation through direct transcriptional activation of
13 Migration 24 WWTR1 and SIAH1 genes. This molecular cascade involves
HIF-1 triggering the ubiquitination and degradation of
14 TGF-beta 24 LATS2, enabling nuclear localization of TAZ. Elevated
15 Endothelial growth-factor 23 expression of both TAZ and HIF-1 target genes correlates
16 Lysyl oxidase 23 with heightened patient mortality, underlining the clinical
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17 Hypoxia-inducible factor-1-alpha 22 relevance of this hypoxia-induced BCSC phenotype .
18 Lung cancer 22 Verteporfin (VP), a photosensitizer and an inhibitor of
19 Resistance 22 YAP/TAZ, has been approved for clinical use to treat
20 Collagen 21 age-related macular degeneration. Furthermore, VP is a
highly specific inhibitor of the Hippo-YAP/TAZ pathway
incorporated in PDT in several cancers. 55-57
and can lead to drug resistance. Hypoxia exacerbates
the phenomenon with the restricted vasculature from 3.6.4. The relationship between breast cancer and
boundary to core in the solid tumor. When tumor cells ECM in TME (green)
are exposed to a hypoxic microenvironment, they become The ECM, microenvironment, and breast cancer are
more resistant and less responsive to clinical treatment. prominent keywords in this cluster, followed by CAFs,
46
Doxorubicin highlights a chemotherapy-associated risk endothelial growth factor, and lysyl oxidase. Breast
and underscores DCAF13 as a promising therapeutic cancer emerges as the most prevalent cancer diagnosis
target to mitigate metastatic risk in breast cancer patients. among women comprising 32% of all cancer cases in
Furthermore, systemic doxorubicin administration post- the cancer estimation by the American Cancer Society
surgery in TNBC induces lung fibroblast expression of in 2024. It is heterogeneous and clinically divided
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complement factors, fostering an immunosuppressive into luminal A-like (Progesterone receptor [PR] and/or
metastatic niche mediated by CAFs and myeloid-derived estrogen receptor [ER] +, human epidermal growth factor
suppressor cells. Nonetheless, combining cytotoxic receptor 2 [HER /neu -), luminal B-like (PR and/or ER +,
2
treatment with complement signaling blockade effectively HER2/neu +), HER2-positive (PR and/or ER -, HER2/neu
alleviates immune dysregulation and lung metastasis, +), and basal-like/triple negative (PR and/or ER -, HER2/
offering a promising therapeutic strategy for TNBC neu -) subtypes classified by the expression of three
patients. 46-48 Immunotherapy is the latest breakthrough pivotal receptors: ER, PR, and HER2. The TME plays a
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in cancer treatment in recent years, but its effectiveness is crucial role in the development of various cancers, and
limited, with only a small number of patients experiencing CAFs are the most abundant component of the TME.
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positive results. The development of nanoparticles (NPs) Activation of CAFs promotes tumor progression. Tang
based on immunotherapy overcomes the heterogeneous et al. discovered that downregulation of the miR-200
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barriers and improves the efficacy in delivery family in breast cancer directly induces the transformation
applications. Panagi et al. repurposed the TGF-β of normal fibroblasts (NFs) into CAFs, leading to ECM
49
50
inhibitor tranilast with Doxil nanomedicine to normalize remodeling. NFs with reduced miR-200 expression exhibit
the TME, improving tumor perfusion, oxygenation, CAF characteristics, enhancing migration and invasion,

Volume 9 Issue 1 (2025) 180 doi: 10.36922/ejmo.7116