NTRK Gene Fusions in Solid Tumors and TRK Inhibitors: A Systematic Review of Case Reports and Case Series

Abstract

The approval of larotrectinib and entrectinib for cancer patients harboring an NTRK gene fusion has represented a milestone in the era of “histology-agnostic” drugs. Among the clinical trials that led to the approval of these two drugs, most of the enrolled patients were affected by soft tissue sarcomas, lung, and salivary gland cancer. However, as next-generation sequencing assays are increasingly available in the clinical setting, health care professionals may be able to detect NTRK gene fusions in patients affected by tumor types under or not represented in the clinical trials. To this aim, we systematically reviewed MEDLINE from its inception to 31 August 2022 for case reports and case series on patients with NTRK gene fusion-positive tumors treated with TRK inhibitors. A virtual cohort of 43 patients was created, excluding those enrolled in the above-mentioned clinical trials. Although our results align with those existing in the literature, various cases of central nervous system tumors were registered in our cohort, confirming the benefit of these agents in this subgroup of patients. Large, multi-institutional registries are needed to provide more information about the efficacy of TRK inhibitors in cancer patients affected by tumor types under or not represented in the clinical trials.

Recent developments in the pathology of primary pulmonary salivary gland‐type tumours

“…185 Head and neck secretory carcinomas have shown response to TRK targeted therapies, [186][187][188] such that the diagnosis of secretory carcinoma in the lung may have implications for predictive biomarker testing and treatment. 189 The bland nuclear features and granularappearing cytoplasm of secretory carcinoma can give it an appearance similar to AciCC. 21,22,190 Positive mammaglobin immunostaining, the presence of mucicarmine-positive secretory material, and negative PAS staining can distinguish secretory carcinoma from AciCC.…”

“…Similarly, approximately 90% of head and neck secretory carcinomas harbour ETV6::NTRK fusions, 184 with a minority showing other fusions that often, but not always, involve ETV6 185 . Head and neck secretory carcinomas have shown response to TRK targeted therapies, 186–188 such that the diagnosis of secretory carcinoma in the lung may have implications for predictive biomarker testing and treatment 189 …”

The Comprehensive Analysis of Specific Proteins as Novel Biomarkers Involved in the Diagnosis and Progression of Gastric Cancer

“…The role of neutrophic thyrosine receptor kinase (NTRK) in GC was assessed in several studies, but it was suggested that the role is marginal as the occurrence of NTRK fusion in GC is very rare [86][87][88]. In spite of this, there is entrectinib, which has anti-cancer activity in GC cells with NTRK overexpression.…”

Histopathological Aspects of The Prognostic Factors for Salivary Gland Cancers

“…Additionally, PDGFR inhibitors target gastrointestinal tumors, glioblastomas, sarcomas, leukemias, and dermatofibrosarcoma protuberans [113]. TRK is encoded by the NTRK gene family (NTRK1, NTRK2, and NTRK3) [114]. This proto-oncogene is responsible for cancer cell transformation, tumor cell proliferation, migration, and invasion.…”