We experimentally validated several actionable findings, including tepotinib to target the IRAK1/4-cholesterol pathway in glioblastoma, brigatinib to target the MARK2/3-Hippo pathway in pancreatic cancer and gilteritinib to overcome MET mutation-driven drug resistance and metastasis. To facilitate exploration of our data, we provide KIRHub, a web-based tool that allows identification of existing inhibitors of wild-type and mutated kinases to guide precision oncology.

However, the observed outcomes should be interpreted within the context of patient selection. The enrichment for prior responders limits the generalizability to unselected post-TKI populations, including those with primary resistance.

The HEATR5B-ALK fusion is targetable by ensartinib, producing durable disease control and excellent tolerability. Comprehensive NGS and ALK IHC are essential for detecting rare actionable ALK variants.

NTRK gene fusions are a critical marker for pediatric soft tissue tumors and are used for precision medicine in these tumors. NTRK gene fusions are used as diagnostic markers for infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinomas, and they play a critical role in the management of these tumors.

The association between the docking predictions and clinical outcomes corroborates the utility of computational modeling for tailoring therapies, although the structural models provide mechanistic insight into drug efficacy against these rare mutations. The present integrated approach emphasizes the value of merging in silico methods into clinical decision-making to overcome the therapeutic uncertainty of uncommon oncogenic driver alterations.

P1, N=24, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Alectinib is the first ALK inhibitor to show a consistent DFS benefit over chemotherapy in patients with resected early-stage ALK-positive NSCLC, regardless of disease stage per AJCC/UICC 7th or 8th edition, nodal status, or tumor size.

The combination of osimertinib and crizotinib resulted in a marked clinical and metabolic response, was well tolerated, and the patient remained in remission. This rare case highlights that acquired CD74-ROS1 fusions may contribute to osimertinib resistance and suggests that combination targeted therapy may represent a potential therapeutic approach in selected patients.

Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.

Due to rapid enrollment, the target sample size was expanded to 28 patients. The primary endpoint is objective response rate confirmed by central assessment; secondary endpoints include duration of response, progression-free survival, overall survival, and safety.Clinical trial registration: jRCT2041210148 (https://jrct.mhlw.go.jp).

In this study, there was no significant difference in the therapeutic effect of alectinib by ALK fusion variants. This finding indicates that alectinib may be an effective treatment option even for patients with V3.