ALK fusion

The Pan Lung Cancer PCR Panel was highly concordant with other assays. The panel can be performed in local laboratories with a rapid turnaround time and represents an attractive alternative to next-generation sequencing for patients with lung cancer.

P=N/A, N=9, Recruiting, Fudan University | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Sep 2025 --> Dec 2026

P1/2, N=20, Recruiting, Tang-Du Hospital | Not yet recruiting --> Recruiting

In addition, germline mutations are present in a subset of patients with mesothelioma and primarily involve genes in the DNA repair and cell cycle regulation and are more common in patients who are young, with family history of mesothelioma, or with peritoneal mesothelioma. In this review, we discuss the considerable heterogeneity of mesothelioma, the diversity of radiologic and gross presentation, various morphologic features with distinctive histologies and ultimately, we individually describe subsets of tumors characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion, as well as the implications of these findings on the diagnostic workup.

High-risk patients classified by 3D VGG-16 model had shorter recurrence-free survival/overall survival (all p < 0.05) and higher prevalence of micropapillary/solid-predominant growth pattern, STAS, and mutations or fusions in KRAS and ALK (all p < 0.05). 3D VGG-16 effectively predicts post-SLR recurrence risk for stage IA ILADC, serving as a potential tool to guide surgical treatment decisions.

RNA sequencing revealed an in-frame fusion between TPM4 Exon 8 and ALK Exon 20. Conservative excision was performed and recurrence has not been observed at one-year follow-up.

While first-generation TRK kinase inhibitors, such as entrectinib and larotrectinib, have shown positive responses in TRK fusion-positive cancers, resistance mutations against these inhibitors in the kinase domain limit their efficacy...By conjugating entrectinib to thalidomide, we identified JWJ-01-378 as a potent and selective cereblon (CRBN)-recruiting degrader of the TPM3-TRKA fusion...TPM3-TRKA degradation by JWJ-01-378 suppressed downstream signaling and reduced cancer cell viability, with improved responses compared to a heterobifunctional control compound that cannot degrade TPM3-TRKA. Together, our study expands the toolbox of selective compounds for evaluating targeted degradation of TRK fusions in diseases including cancer.

Pralsetinib was added to osimertinib, resulting in a response lasting 4 months...After one month with alectinib only, osimertinib was added due to the progression, resulting in another response of more than two months. Upon progression with quadruple alterations (EGFR 19del, EGFR C797S, MET amplification, and RET fusions), cabozantinib-gefitinib combination was initiated, leading to rapid deterioration...At the same time, comprehensive genomic testing remains essential for therapeutic decision-making, with ctDNA analysis complementing tissue-based approaches. Notably, the FGFR3-TACC3 fusion may represent a novel resistance mechanism contributing to the limited efficacy of EGFR-TKI.

Small-molecule ALK inhibitors, including crizotinib, have demonstrated high overall response rates (67%-88%) and complete remission rates (~60%-80%) in relapsed or refractory ALK-positive ALCL, often with rapid clinical responses...In addition, it explores emerging strategies for integrating ALK inhibitors into precision-based management of T-cell lymphomas, including combination approaches with chemotherapy, immunotherapy or antibody-drug conjugates. Collectively, these developments highlight a paradigm shift towards biology-driven, personalized therapy in ALK-positive ALCL.

P2, N=100, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Phase classification: P3 --> P2 | N=280 --> 100 | Trial completion date: Mar 2031 --> Dec 2027 | Trial primary completion date: Aug 2027 --> Dec 2026

This case highlights the importance of genetic profiling and rapid and substantial efficacy of alectinib in treating ALK-positive PLADC, reinforcing the role of ALK inhibitors in managing severe cases and offering valuable insights for clinical strategies.

P2, N=54, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China