Endothelin-axis antagonism enhances tumor perfusion in pancreatic cancer

Gautam, Shailendra K.; Dalal, Vipin; Sajja, Balasrinivasa R.; Gupta, Suprit; Gulati, Mansi; Dwivedi, Nidhi V; Cox, Jesse L.; Rachagani, Satyanarayana; Liu, Yutong; Chung, Vincent; Salgia, Ravi; Batra, Surinder K.; Jain, Maneesh

doi:10.1016/j.canlet.2022.215801

Cited by 5 publications

(2 citation statements)

References 93 publications

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“…The addition of an ETBR agonist to the treatment was an attempt to improve drug penetration and distribution in the tumor, as failure to achieve adequate cytotoxic concentrations in the tumor has been identified as a potential mechanism mediating treatment failure in bile duct cancer. However, the preclinical data on the improvement of tumor perfusion by ETBR are unclear: the EBTR agonist IRL-1620 improves tumor perfusion in some animal models of [ 136 , 137 ] and causes severe vasoconstriction in other [ 138 , 139 ], whereas bosentan, a dual ETR antagonist, significantly improved tumor perfusion in pancreatic cancer [ 77 ]. In addition to a high incidence of grade 3 or 4 adverse events, the trial was terminated prematurely because the pre-specified goal of a median progression-free survival of 5 months could not be achieved.…”

Section: Further Approachesmentioning

confidence: 99%

Endothelin and the tumor microenvironment: a finger in every pie

Arndt,

Turkowski,

Cekay

et al. 2024

Clinical Science

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The tumor microenvironment (TME) plays a central role in the development of cancer. Within this complex milieu, the endothelin (ET) system plays a key role by triggering epithelial-to-mesenchymal transition, causing degradation of the extracellular matrix and modulating hypoxia response, cell proliferation, composition, and activation. These multiple effects of the ET system on cancer progression have prompted numerous preclinical studies targeting the ET system with promising results, leading to considerable optimism for subsequent clinical trials. However, these clinical trials have not lived up to the high expectations; in fact, the clinical trials have failed to demonstrate any substantiated benefit of targeting the ET system in cancer patients. This review discusses the major and recent advances of the ET system with respect to TME and comments on past and ongoing clinical trials of the ET system.

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Section: Further Approachesmentioning

confidence: 99%

Endothelin and the tumor microenvironment: a finger in every pie

Arndt,

Turkowski,

Cekay

et al. 2024

Clinical Science

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“…Candesartan and bosentan (ET-receptor antagonists, which significantly lower blood pressure in patients with essential hypertension) are in Phase I clinical trials for pancreatic cancer combined with gemcitabine and other therapeutic agents ( Figure 4 ). It has been reported that a potential strategy to selectively enhance tumor perfusion and improve therapeutic agents’ delivery in pancreatic tumors relies on targeting the ET axis [ 126 ]. Bosentan exerts antifibrotic and anti-cancer effects in vitro by inhibiting pancreatic stellate cells (PSC) and DSL6A pancreatic cancer cell proliferation and collagen synthesis in PSC [ 127 ].…”

Section: Repurposing Of Anti-hypertensive and Anti-diabetic Drugs: Cu...mentioning

confidence: 99%

Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp

Hijazi

Gessner

El‐Najjar

2023

Cancers

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Despite the advancement in drug discovery for cancer therapy, drug repurposing remains an exceptional opportunistic strategy. This approach offers many advantages (faster, safer, and cheaper drugs) typically needed to overcome increased challenges, i.e., side effects, resistance, and costs associated with cancer therapy. However, not all drug classes suit a patient’s condition or long-time use. For that, repurposing chronically used medications is more appealing. This review highlights the importance of repurposing anti-diabetic and anti-hypertensive drugs in the global fight against human malignancies. Extensive searches of all available evidence (up to 30 March 2023) on the anti-cancer activities of anti-diabetic and anti-hypertensive agents are obtained from multiple resources (PubMed, Google Scholar, ClinicalTrials.gov, Drug Bank database, ReDo database, and the National Institutes of Health). Interestingly, more than 92 clinical trials are evaluating the anti-cancer activity of 14 anti-diabetic and anti-hypertensive drugs against more than 15 cancer types. Moreover, some of these agents have reached Phase IV evaluations, suggesting promising official release as anti-cancer medications. This comprehensive review provides current updates on different anti-diabetic and anti-hypertensive classes possessing anti-cancer activities with the available evidence about their mechanism(s) and stage of development and evaluation. Hence, it serves researchers and clinicians interested in anti-cancer drug discovery and cancer management.

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FABP4 in macrophages facilitates obesity-associated pancreatic cancer progression via the NLRP3/IL-1β axis

Yang,

Liu,

et al. 2023

Cancer Letters

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Endothelin-axis antagonism enhances tumor perfusion in pancreatic cancer

Cited by 5 publications

References 93 publications

Endothelin and the tumor microenvironment: a finger in every pie

Endothelin and the tumor microenvironment: a finger in every pie

Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp

FABP4 in macrophages facilitates obesity-associated pancreatic cancer progression via the NLRP3/IL-1β axis

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