Publications by authors named "C Zanna"
Article Synopsis
- - This study evaluated the safety and effectiveness of Debio 1347, a new oral drug targeting FGFR fusions in patients with advanced solid tumors, focusing on its ability to produce objective responses and other outcomes in different cancer types.
- - A total of 63 patients participated, with only a 5% objective response rate, leading to the trial's early termination due to lower-than-expected effectiveness, despite manageable side effects like hyperphosphatemia and stomatitis.
- - The findings suggest that while the drug has some tolerance, its lack of significant efficacy means it should not undergo further testing for FGFR fusion tumors; the study also provided insight into the characteristics of FGFR fusions in solid tumors.
Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non-responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous.
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- - Cancer cells produce a protein called IF, which helps them survive during low oxygen conditions (ischemia) by inhibiting ATP synthase, important for energy production.
- - Researchers found that IF enhances the survival and growth of bone and colon cancer cells during stress conditions, through processes like mitophagy (recycling damaged mitochondria) and mitochondrial biogenesis (creating new mitochondria).
- - Reducing the activity of IF could be a potential treatment strategy for tumors that depend on oxygen-based energy production, as it may inhibit their growth under low oxygen conditions.
Leber's hereditary optic neuropathy (LHON), a disease associated with a mitochondrial DNA mutation, is characterized by blindness due to degeneration of retinal ganglion cells (RGCs) and their axons, which form the optic nerve. We show that a sustained pathological autophagy and compartment-specific mitophagy activity affects LHON patient-derived cells and cybrids, as well as induced pluripotent-stem-cell-derived neurons. This is variably counterbalanced by compensatory mitobiogenesis.
View Article and Find Full Text PDFXevinapant is a first-in-class antagonist of inhibitor of apoptosis proteins, which enhances cancer cell sensitivity to chemotherapy and radiotherapy. In a phase II randomized study in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), xevinapant plus standard-of-care cisplatin-based chemoradiotherapy (CRT) showed superior efficacy versus placebo plus CRT. Here, we describe the design of TrilynX (NCT04459715), a randomized, double-blind, phase III study.
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