TPM3 (Tropomyosin 3)

Here, we report a lung IMT in a 45-year-old female demonstrating a unique meningothelial-like pattern, equivocal ALK expression (negative for clone 5A4 and positive for clone ALK1), negative ALK rearrangement by FISH, and the presence of the TPM3::ALK fusion. To our knowledge, this is the first reported case of lung IMT displaying meningothelial-like whorls, with a particular focus on differential diagnosis.

EZR links cytoskeletal remodeling to STAT3 signalling to drive metastatic competence and paclitaxel resistance, nominating EZR as a potential therapeutic vulnerability in treatment-refractory breast cancer.

Moreover, we demonstrated that Suramin effectively suppressed CC tumor growth by inhibiting PFKP-mediated glycolysis. Our findings provide a robust prognostic model and disclose PFKP as a potential therapeutic target in CC, offering insightful guidance on cancer management of CC patients.

Pediatric ALK+ ALCL with non-NPM1-ALK fusions exhibits diverse clinical features and outcomes. TPM3-ALK fusions might correlate with a more favorable course, while other variants may face a potentially higher relapse risk. ALK inhibitors showed promising efficacy in the salvage setting. These preliminary findings highlight the need for larger prospective studies to validate mutation-specific risk stratification and therapeutic strategies.

This case underscores the importance of integrating molecular diagnostics into the evaluation of atypical spindle cell tumors, particularly those presenting with aggressive clinical features despite low-grade histology. Early identification of NTRK fusions enables timely initiation of TRK inhibitor therapy, offering durable disease control and functional recovery. Broader awareness and implementation of molecular testing can greatly enhance the management of rare pediatric sarcomas.

The patient remains stable with no evidence of local, nodal, or metastatic disease for more than three years following the initial presentation. This report aims to propose the use of larotrectinib as a management option for recurrent NTRK-positive cervical sarcomas.

Mechanistically, TPM3-TRKA degradation by compound 9 was dependent on CRBN-mediated polyubiquitination and proteasomal degradation; accordingly, it was hindered by inhibitors of the proteasome (MG132) or Cullins (MLN4924), by dominant negative Cullin 4A mutant, and by free pomalidomide. Finally, a compound 9 derivative, compound 20, induced in vivo degradation of TMP3-TRKA in KM12 cells mouse xenografts. In conclusion, our study indicated that PROTAC-mediated degradation is an efficient strategy to intercept RET and TRKA oncogenic signaling.

By synthesizing current evidence, this review aims to provide insights into the diagnostic, prognostic, and therapeutic landscape of TPM3-related gene fusions, fostering advancements in precision oncology.

Furthermore, ATM-3507 markedly reduced CXCL12-stimulated chemotaxis and integrin-dependent motility of DLBCL cell lines on fibronectin. Tpm3.1/3.2 orchestrates key actin-driven processes in B cells, and drugs that target Tpm3.1/3.2 may be useful adjuncts for treating DLBCL.

P1/2, N=30, Not yet recruiting, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School; Nanjing Drum Tower Hospital, The Affiliated Hospital of Nan

Drug sensitivity assays revealed an IC₅₀ of 64.0 nM for entrectinib and 806.8 nM for osimertinib, indicating reduced sensitivity to EGFR inhibition. We provided experimental evidence for that TPM3-NTRK1 fusions can mediate acquired resistance to osimertinib in a new lung adenocarcinoma cell line. LUNK1 represents a useful preclinical model for investigating resistance mechanisms and assessing dual-targeted treatment strategies.

Our study provides new insights into the biology and management of NTRK-rearranged spindle cell tumors, contributing to the expanding evidence supporting the use of TRK inhibitors in these tumors. Further studies are needed to validate our findings and to explore the potential of second-generation TRK inhibitors in overcoming resistance.