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In contrast, the combination of CB-839/telaglenastat with multiple tyrosine kinase receptor inhibitor cabozantinib did not improve the efficacy of cabozantinib in patients with advanced RCC in the CANTATA phase II randomized clinical trial (NCT03428217), although it was well tolerated [163]

Research has shown that ER stress-induced trypsin-like activity promotes the release of the inflammatory mediator C-X-C chemokine ligand 8 (CXCL8), thereby exacerbating the inflammatory process [89]

5.2.4 Polyphenol oxidases (PPOs) PPOs are omnipresent Cu-containing enzymes which utilize molecular Oxygen for catalytic hydroxylation and dehydrogenation of o- diphenolic compounds like catechol and caffeic acid to their respective quinones, which leads to the alkylation of nucleophilic groups and self-polymerization to produce dark-coloured melanin polymers [185]

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