ANTIANGIOGENESIS STRATEGIES REVISITED: FROM STARVING TUMORS TO ALLEVIATING HYPOXIA
By Rakesh K. Jain. Cancer Cell, 2014
1,447 citations recorded by the source corpus.
Ten antiangiogenic drugs targeting VEGF or its receptors are approved for cancer treatment. However, these agents, intended to block tumors’ blood supply, may cause hypoxia, which may fuel tumor progression and treatment resistance. Emerging clinical data suggest that patients whose tumor perfusion or oxygenation increases in response to these agents may actually survive longer. Hence, strategies aimed at alleviating tumor hypoxia while improving perfusion may enhance the outcome of radiotherapy, chemotherapy, and immunotherapy. Here, I summarize lessons learned from pre-clinical and clinical studies over the past decade and propose strategies for improving antiangiogenic therapy outcomes for malignant and nonmalignant diseases.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/44be070726fe34a847e937f0a1829ec65219f41c
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Citations in the corpus
- Angiogenic signaling pathways and anti-angiogenic therapy for cancer (2023, background): “Traditional anti-angiogenic therapy on the basis of “starving tumors”, which obstructed the energy supply for tumor tissue by blocking angiogenesis to guide the death of tumor cells.(366) In 2004, the first anti-angiogenic drug bevacizumab (Table 1) approved by FDA significantly prolonged the PFS ra”
- VEGF in Signaling and Disease: Beyond Discovery and Development (2019, background): “1256 Cell 176, March 7, 2019 VEGF-blocking agents may be associated with hypoxia and followed by tissue damage and other detrimental effects (Jain, 2014).”
- Role of hypoxia in cancer therapy by regulating the tumor microenvironment (2019, neutral): “to tumor progression and therapeutic resistance [43, 44].”
- Physical traits of cancer (2020, background): “Vessel compression contributes to hypoxia (15, 16) and interferes with the delivery and/or efficacy of chemo-, radio-, and immunotherapies (17, 18).”
- Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy (2020, background): “Hypoxia again is directly linked to resistance vs. various forms of cytotoxic therapy and radiotherapy (Moeller and Dewhirst, 2004; Doublier et al., 2012; Jain, 2014; Horsman and Overgaard, 2016; Graham and Unger, 2018).”
- Intratumor heterogeneity: the Rosetta stone of therapy resistance (2020, background): “While antiangiogenic agents did not live up to the initial promise of eliminating tumors by blocking their access to oxygen/nutrients, the reverse idea – normalizing blood vasculature using lower doses of anti-angiogenic drugs, might still prove to be clinically useful (Jain, 2014).”
- Tumor angiogenesis and vascular normalization: alternative therapeutic targets (2017, background): “Another challenge in the use of VEGF inhibitors to obtain vascular normalization is achieving what has been referred to as a ‘‘window of opportunity,’’ which is the time frame and dosage of VEGF inhibitor administration required to observe normalization of tumor blood vessels [5].”
- Combined antiangiogenic and anti–PD-L1 therapy stimulates tumor immunity through HEV formation (2017, background): “Notwithstanding the favorable effects of these inhibitors in some patients, they improve progression-free survival and quality of life, but are unfortunately short-lived and modestly influence overall survival in most patients (12, 15, 16).”