ROS1 positive

The last follow-up in August 2025 showed the patient remained in good survival status. This case highlights a novel strategy of neoadjuvant targeted downstaging followed by surgical resection for small-lesion, highly invasive NSCLC, as well as the potential value of integrating postoperative Chinese-Western medicine management for long-term survival and treatment tolerance.

We found progressive arthropathy, mostly painless, in one or more joints or intervertebral spaces of patients receiving crizotinib for NSCLC.

Multiple ROS1 tyrosine kinase inhibitors (TKIs)-from crizotinib to newer agents such as entrectinib, lorlatinib, repotrectinib, taletrectinib, and the highly selective zidesamtinib-have improved systemic and intracranial outcomes, although resistance remains inevitable and biologically diverse, involving both on-target kinase mutations and off-target mechanisms...Pemetrexed-based chemotherapy remains an effective option, whereas immune checkpoint inhibitors provide limited benefit...Looking ahead, priorities include optimizing sequencing strategies, evaluating perioperative targeted approaches, and incorporating genomic monitoring to anticipate resistance. These advances are reshaping the natural history of ROS1-rearranged NSCLC and supporting a more durable, precision-driven treatment paradigm.

In ROS1-positive NSCLC patients, taletrectinib has been effective and well tolerated, as evidenced by early clinical trials, including those that are resistant to crizotinib. It demonstrates potential for disease control, as it has excellent oral absorption and is able to combat the spread of neurological disorders. Taletrectinib is emerging as a promising candidate for enhancing the outcomes of patients with ROS1-positive lung cancer as the treatment landscape for this disease continues to evolve.

In this study, in addition to the induction of apoptosis, the use of PARPis (olaparib and niraparib) as maintenance therapies inhibited cell proliferation by causing cellular senescence to exert potent anticancer effects on Capan-1 (BRCA mutated) and PANC-1 (BRCA wild-type) cells...The inhibition of Bcl-2 through the sequence-dependent combination of navitoclax enhanced the anticancer effects of PARPis by removing senescent cells. Collectively, data from our study demonstrate that the clinical application of PARPis as maintenance therapy could be achieved through the induction of cellular senescence. Furthermore, sequence-dependent combination with senescence-targeting drugs can potentiate pancreatic cancer treatment effects of PARPis regardless of the BRCA status.

Because these disorders may be limited to the skin or be a manifestation of a systemic histiocytic neoplasm, correlation with clinical features is essential. Molecular genetic analysis to identify mutations in the mitogen-activated protein kinase pathway should be considered to provide options for targeted therapy.

P=N/A, N=35, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=500 --> 35 | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P3, N=71, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

Approximately 9% of GBMs harbor targetable fusions, with five genes (FGFR3, MET, EGFR, NTRK2, PDGFRA) comprising 8%. These findings support multi-arm clinical trials to evaluate targeted therapies, potentially improving outcomes for molecularly defined GBM subgroups.

The condition exhibited a typical positive rechallenge feature of "discontinuation and recurrence," providing critical clinical evidence to establish this causal relationship. The case aims to enhance the understanding of crizotinib's metabolic side effects, underscores the importance of dynamic lipid monitoring, and offers empirical support for the standardized management of such rare adverse reactions.

NBTE may be the first sign of malignancy and should be considered in patients with embolism and sterile valve lesions. M-TEER can stabilize high-risk patients and enable timely, potentially curative cancer treatment.

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.