Publications by authors named "C Vellano"
Article Synopsis
- Exploiting TRAILR2 activation could improve cancer treatments, but past therapies faced issues like low effectiveness and liver damage.
- The new TR2/CDH3 BAB antibody targets both CDH3 and TRAILR2, enhancing apoptosis specifically in tumor cells expressing CDH3, showcasing effectiveness in various cancers and CRISPR-engineered models.
- In pancreatic cancer, where current treatments are lacking, TR2/CDH3 BAB shows promise, especially when used with other chemotherapy drugs, indicating potential for effective cancer therapy with a good safety profile.
Combination approaches are needed to strengthen and extend the clinical response to KRAS inhibitors (KRASi). Here, we assessed the antitumor responses of KRAS mutant lung and colorectal cancer models to combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus the KRAS inhibitor, adagrasib. We found that responses to BI-3406 plus adagrasib were stronger than to adagrasib alone, comparable to adagrasib with SHP2 (SHP2i) or EGFR inhibitors and correlated with stronger suppression of RAS-MAPK signaling.
View Article and Find Full Text PDFPurpose: Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.
Experimental Design: We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models.
Article Synopsis
- Researchers are exploring combination therapies to enhance the effectiveness of KRAS targeted therapy in cancer treatment.
- The study shows that combining the SOS1-KRAS inhibitor BI-3406 with a KRAS inhibitor yields a stronger anti-tumor response than using either treatment alone or other combinations in lung and colorectal cancer models.
- This combination not only suppresses key cancer signaling pathways more effectively but also helps delay drug resistance, making it a promising strategy for tackling KRAS-mutated tumors and overcoming resistance to KRAS inhibitors.
Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). The primary endpoints were safety, tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D) of IACS-010759.
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