Xalkori (crizotinib)

On this basis, we developed IR788-Crizotinib, a c-Met-targeted near-infrared window-II (NIR-II) fluorescent probe, and evaluated its imaging performance in subcutaneous xenograft, 4-NQO-induced oral lesion, orthotopic tongue OSCC and lymph node metastasis mouse models...In cervical lymph nodes, it detected micro-metastatic foci as small as 342 μm, with 100% sensitivity. c-Met-targeted NIR-II imaging provides an integrated visualization strategy for premalignant lesion screening, primary tumor delineation and metastatic lymph node detection in OSCC, with translational potential for precision management of oral cancer.

Then the patient was recommended ALK-TKIs treatment after detecting ALK rearrangement, and achieved complete response (CR) from a second-generation ALK-TKI inhibitor, iruplinalkib, after resistance to the first-generation inhibitor crizotinib. This is the first case of iruplinalkib achieved therapeutic success in uterine IMT, suggesting that a sequential ALK-TKIs with iruplinalkib could be an optimal targeted therapeutic strategy for ALK-rearranged IMTs.

Crizotinib showed no significant difference in progression-free survival (PFS) or overall survival (OS) between first-line and post-chemotherapy use (PFS: p = 0.803; OS: p = 0.761). For second-generation ALK-TKIs, first-line treatment had numerically longer PFS compared to post-chemotherapy (alectinib: 41 vs 24 months; ceritinib: 30 vs 8 months), but these differences were not statistically significant after adjustment (p = 0.120 and 0.284, respectively)...Among patients treated with alectinib, there appears to be a trend toward shorter PFS and OS in those with MET overexpression. In a limited number of matched samples, PD-L1 expression did not change significantly after TKI resistance, although a slight increase was observed.

ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib has significantly improved clinical outcomes in ALK-rearranged NSCLC patients. To overcome these resistance mechanisms, the development of novel therapeutic strategies are required. By integrating structural biology, mutation evolution patterns, and emerging therapeutic approaches, this review underscores the need for next-generation inhibitors to overcome resistance and improve long-term outcomes in patients with ALK-positive NSCLC.

Since the approval of crizotinib, which was the first ALK tyrosine kinase inhibitor (TKI), the treatment landscape has rapidly evolved with the development of multiple next-generation TKIs and investigational agents...However, CNS progression, acquired resistance, and optimal treatment sequencing continue to limit outcomes. This review synthesizes current evidence to guide clinical practice and future investigations.

This multicentre real-world cohort describes longitudinal ROS1 management with evolving treatments. Favourable survival likely reflects reflex molecular testing, access to ROS1i, and high clinical trial enrolment.

Crizotinib prolonged the QT interval and increased susceptibility to ventricular arrhythmias by suppressing cAMP-PKA activity and thereby downregulating KCNH2. Pharmacological activation of cAMP signaling mitigated crizotinib-induced acquired QT prolongation.

Transcriptomic analyses identified PIP5K1C as a downstream effector regulated through a competitive endogenous RNA mechanism in which circZBTB46 acts as a sponge to miR-25-3p, alleviating its repression of PIP5K1C. These findings uncover a previously unrecognized mechanism of drug resistance in ALK( + ) ALCL and establish circZBTB46 as a promising therapeutic target.

Clinical courses were heterogeneous: one patient achieved a durable partial response using combined osimertinib and crizotinib. A second patient, intolerant to dual TKI therapy due to QTc prolongation and grade 3 edemas, achieved a sustained partial response with platinum-pemetrexed chemotherapy...However, its biological significance, driver versus passenger role, and therapeutic relevance remain uncertain. Combined EGFR and ROS1 inhibition may be considered in selected cases, but further validation is required.

This multinational registry-based analysis highlights evolving global treatment patterns, supports newer TKIs' effectiveness, and identifies clinical and molecular factors associated with treatment duration.

The efficacy of tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, lorlatinib, entrectinib, and repotrectinib was systematically evaluated. Our findings underscore that although G2032R and L2026M mutations reside within the kinase active site, their impact extends far beyond steric hindrance, altering overall kinase domain dynamics. Collectively, these data establish a robust panel of patient-derived ROS1 cell lines that recapitulate clinical resistance patterns and, together with complementary computational modeling, provide a valuable framework to dissect ROS1 tumor biology and support rational design of next-generation inhibitors.