AZD 0424 / AstraZeneca, Cancer Research UK - LARVOL DELTA

Hair loss in cancer patients receiving small molecule inhibitors: Evidence from clinical trials (AACR 2026) - "Hedgehog pathway inhibitors induced the highest overall rates, ranging from 20-30% with saridegib and glasdegib, and up to 63% with vismodegib. FGFR inhibitors (pemigatinib, infigratinib) and other kinase inhibitors (ripretinib, vemurafenib, sorafenib, AZD0424) demonstrated moderate rates (22-48%). Lower alopecia incidence was reported with aromatase inhibitors (anastrozole, lenostrozole) and the aurora B kinase inhibitor BI 811283, ranging from 9 to 21%...The higher incidences seen with Hedgehog inhibitors, compared with aromatase inhibitors, highlight how pathway-specific disruption of follicular signaling contributes to hair loss. Further research into the molecular mechanisms of these agents may help clinicians better anticipate and manage this side effect."

Clinical • Oncology • BRAF

Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors for cancer treatment. (PubMed, Mol Oncol) - "We demonstrate that SRC is activated in response to treatment of KRAS-mutant colorectal cell lines with MEK inhibitors (trametinib or AZD6244), and that AZD0424 abrogates this. We also demonstrate that drug-induced resistance to trametinib is not re-sensitised by AZD0424 treatment in vitro, likely as a result of multiple compensatory signalling mechanisms; however, inhibition of SRC remains an effective way to block invasion of trametinib-resistant tumour cells. These data imply that SRC inhibition may offer a useful addition to MEK-inhibitor combination strategies."

Combination therapy • Journal • Oncology • EGFR • KRAS