P1, N=5, Active, not recruiting, City of Hope Medical Center | Trial completion date: Apr 2026 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Mar 2027

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.

Among the tested compounds, entrectinib exhibited consistently strong binding affinities across all variants (-9.7 to -10.7 kcal/mol), whereas reduced binding affinities were observed for several inhibitors against E734K, A756D, and R897G variants...Clinical databases reported that p.Met918Thr (pathogenic) and p.Arg897Gln (risk factor) emerged as significant variants linked to MEN2-related cancers and Hirschsprung disease. As a conclusion, this integrative in silico study identifies deleterious RET nsSNPs with potential structural, functional, and therapeutic significance providing mechanisms for precision oncology and future clinical investigation.

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.

P4, N=29, Not yet recruiting, Hunan Cancer Hospital

P=N/A, N=160, Not yet recruiting, Sun Yat-sen University

After an uneventful 5-day hospitalization without complications, the patient remains disease-free at the 12-month follow-up. This is the first report of neoadjuvant lorlatinib followed by uniportal VATS achieving pCR predicted by CMR in stage IIIB ALK-positive NSCLC, given the limitations of short-term follow-up and a single-case design.

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.

P4, N=80, Not yet recruiting, Qiming Wang