ROS1 positive

Current first-generation tyrosine kinase inhibitors (TKIs) such as crizotinib and entrectinib provide meaningful benefit but are limited by poor central nervous system (CNS) penetration and the development of resistance mutations, particularly G2032R. While its approval represents a significant advance for ROS1+ NSCLC, challenges remain, including resistance mechanisms such as L2086F, limited global access, and the absence of phase III confirmatory trials. Ongoing research into sequencing strategies, resistance profiling, and novel combination regimens will be essential to optimize patient outcomes.

Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) calculations further confirmed that yibeinoside A and vomicine had better binding free energies than lorlatinib. Collectively, these findings suggest that yibeinoside A, with its balanced binding interactions and favorable predicted pharmacokinetic profile, is a promising lead candidate for further development as a selective inhibitor against G2032R-mutant ROS1.

Repotrectinib is not cost-effective at current prices, but first-line use is consistently more economically favorable than second-line therapy. Price reductions or shorter treatment durations could improve its cost-effectiveness.

P2, N=70, Active, not recruiting, CStone Pharmaceuticals | Trial completion date: Nov 2025 --> May 2026

P=N/A, N=42, Recruiting, Peking University

Extranodal RDD involving the breast is exceedingly rare and can mimic carcinoma both clinically and radiologically. Accurate diagnosis requires histologic and immunohistochemical confirmation.

Alectinib yielded a median PFS of 18.6 months and OS of 29.8 months in ALK-positive patients, while crizotinib produced a median PFS and OS of 7 months in ROS1-positive patients. Although targeted therapies prolonged PFS compared with chemotherapy, this improvement did not translate into a significant OS advantage, likely influenced by retrospective design and treatment crossover. Findings represent real-world outcomes in a molecularly defined subgroup.

Crizotinib showed limited efficacy with a median progression-free survival of 3.5 months. These findings highlight indolent disease behavior but limited TKI benefit, supporting the need for adjuvant trials.

P1, N=168, Completed, AbbVie | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Sep 2025 | Trial primary completion date: Jun 2025 --> Sep 2025

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.