Reactive resistance to anti-angiogenic drugs

Bousquet, Guilhem; Janin, Anne

doi:10.18632/aging.100748

Cited by 2 publications

(1 citation statement)

References 7 publications

(8 reference statements)

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“…In view of development of secondary hypoxia limiting the effectiveness of current therapy, anti-angiogenic agents should perhaps be combined with renal CSC- targeting drugs. In addition, an innovative therapeutic perspective might be the use of hyperoxia/hyperbaric oxygen to decrease the number of CSCs in resistant metastases (e.g., due to restoration of more differentiated phenotype), resensitizing them [ 265 ]. Moreover, a highly challenging issue is counteracting hypoxia-related limitations of anti-angiogenic drugs by tumor vessel normalization (restoration of healthy vasculature) using ITPP [ 266 ] and a soluble form of VEGFR-2 [ 267 ] in order to inhibit CSC selection and improve treatment efficiacy.…”

Section: Conclusion Therapeutic Implications and Future Directionsmentioning

confidence: 99%

The Role of Hypoxia and Cancer Stem Cells in Renal Cell Carcinoma Pathogenesis

Myszczyszyn¹,

Czarnecka²,

Matak

et al. 2015

Stem Cell Rev and Rep

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The cancer stem cell (CSC) model has recently been approached also in renal cell carcinoma (RCC). A few populations of putative renal tumor-initiating cells (TICs) were identified, but they are indifferently understood; however, the first and most thoroughly investigated are CD105-positive CSCs. The article presents a detailed comparison of all renal CSC-like populations identified by now as well as their presumable origin. Hypoxic activation of hypoxia-inducible factors (HIFs) contributes to tumor aggressiveness by multiple molecular pathways, including the governance of immature stem cell-like phenotype and related epithelial-to-mesenchymal transition (EMT)/de-differentiation, and, as a result, poor prognosis. Due to intrinsic von Hippel-Lindau protein (pVHL) loss of function, clear-cell RCC (ccRCC) develops unique pathological intra-cellular pseudo-hypoxic phenotype with a constant HIF activation, regardless of oxygen level. Despite satisfactory evidence concerning pseudo-hypoxia importance in RCC biology, its influence on putative renal CSC-like largely remains unknown. Thus, the article discusses a current knowledge of HIF-1α/2α signaling pathways in the promotion of undifferentiated tumor phenotype in general, including some experimental findings specific for pseudo-hypoxic ccRCC, mostly dependent from HIF-2α oncogenic functions. Existing gaps in understanding both putative renal CSCs and their potential connection with hypoxia need to be filled in order to propose breakthrough strategies for RCC treatment.

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Section: Conclusion Therapeutic Implications and Future Directionsmentioning

confidence: 99%