ROS1 positive

This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced ROS1-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.

The GSK-3ß inhibitor and Actinonin combination demonstrated a powerful tumor-suppressive effect in vivo without severe side effects. Combining GSK-3ß inhibition with Actinonin can effectively eliminate cancer cells with HNF-1ß overexpression by inhibiting glycolysis and promoting mitochondrial turnover, highlighting new options for cancer therapy.

In summary, the current study highlighted that RPLP0 establishes a feedback circuit with c‑Myc by facilitating JAK2/STAT3 pathway activation through suppressing ROS levels, while c‑Myc reciprocally activates RPLP0, forming a regulatory circuit loop that drives HCC progression. Thus, targeting the c‑Myc/RPLP0/ROS/JAK2/STAT3 axis emerges as a promising therapeutic strategy for the management of HCC.

Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. In this nonrandomized clinical trial, lorlatinib demonstrated durable efficacy and manageable safety in TKI-naive advanced ROS1-positive NSCLC, supporting the potential for using lorlatinib in earlier treatment settings. ClinicalTrials.gov Identifier: NCT03612154.

Crizotinib first demonstrated substantial clinical benefit, but its limitations, including poor central nervous system (CNS) penetration and acquired resistance, highlighted the need for next-generation inhibitors. Several agents have since been developed, including entrectinib, lorlatinib, repotrectinib, taletrectinib, and zidesamtinib, each offering improved intracranial (IC) activity and efficacy against resistance mutations, notably ROS1^G2032R. Despite these advances, optimal sequencing strategies remain undefined, and resistance ultimately emerges in most patients. This review provides an updated overview of ROS1 biology, diagnostic approaches, clinical outcomes with currently available TKIs, mechanisms of resistance, and ongoing challenges, emphasizing the rapidly evolving therapeutic landscape.

The safety profile of crizotinib remained consistent with previous reports, with most adverse events being grade 1 or 2 and no new safety concerns identified. This analysis supports the efficacy of crizotinib in patients with advanced NSCLC and ROS1 rearrangements, although its activity in patients with BM remains limited, highlighting the need for brain-penetrant tyrosine kinase inhibitors to improve outcomes in this patient group.

The patient received first-line chemotherapy with pemetrexed (820 mg on day 1) plus cisplatin (40 mg on days 1-3) every 21 days and achieved a remarkable progression-free survival (PFS) of 48 months...She was subsequently treated with ensartinib (225 mg once daily), yielding a favorable response...Unless there are studies with large cohorts clarifying the case, an individualized regimen-potentially starting with chemotherapy and transitioning to targeted agents-may be justified. Further clinical experience and collaborative research are essential to develop evidence-based guidelines for this exceptionally rare subset.

This real-world analysis highlighted durable effectiveness of lorlatinib in treating NSCLC patients with ROS1 rearrangements in second-line and beyond settings. The safety profile aligned with previous clinical and real-world studies.

Findings show that taletrectinib has a promising anticancer impact, good CNS penetration, and a solid safety record, especially in patients with brain metastases. These results imply that ROS1-positive cancers may benefit from taletrectinib as a treatment.

P3, N=210, Not yet recruiting, Shanghai Oriental Hospital; Fosun Wanbang (Jiangsu) Pharmaceutical Group Co., Ltd.

P2, N=80, Recruiting, Zhejiang cancer Hospital; Zhejiang Cancer Hospital