A rare case of recurrent ovarian cancer with TPM3‑NTRK1 gene rearrangement: A case report

Abstract

NTRK gene fusion is rare in gynecological cancer. Entrectinib is a novel targeted drug, which is a potent inhibitor of TRK A, B and C. The present case report described a case of recurrent ovarian cancer with TPM3-NTRK1 rearrangement, which was detected by next-generation sequencing (NGS) and treated with entrectinib. A 56-year-old woman was diagnosed as having stage IV ovarian cancer with positive pleural fluid cytology. Neoadjuvant chemotherapy and interval debulking surgery, followed by chemotherapy, were performed. A total of 10 months after completion of chemotherapy, the disease recurred and the patient was treated with multimodal therapy for recurrence. DNA-based NGS detected TPM3-NTRK1 rearrangement and entrectinib therapy was initiated; however, the disease progressed despite 6 weeks of entrectinib administration, and 1 month after discontinuation of entrectinib, the patient died. After their death, immunohistochemistry with a pan-Trk monoclonal antibody was performed to determine the expression levels of TRK; however, immunohistochemistry was negative for TRK. In conclusion, the present case report described a rare case of recurrent ovarian cancer with TPM3-NTRK1 gene fusion, in which entrectinib was not effective. While NTRK gene fusion was detected by DNA-based NGS, immunohistochemistry was negative for TRK. These findings indicated that immunohistochemistry may be required for confirmation of TRK protein expression prior to entrectinib administration.

Real‐world experience of tropomyosin receptor kinase inhibition with entrectinib in ETV6‐NTRK3 positive metastatic salivary secretory carcinoma: A case series

“…Such excellent clinical efficacy seems to be consistent with a pooled analysis of phase I/II trials of entrectinib and larotrectinib in SGMs 7,9 . However, previous case reports on entrectinib have mainly focused on ovarian cancer, 10 pediatric high‐grade glioma 11,12 soft tissue tumors, neuroendocrine tumor, 13 pancreatic cancer, glioneuronal tumor, 14 and NSCLC 15 . Thus, precise case‐by‐case information on the efficacy of entrectinib for SGMs is limited.…”

Entrectinib use in a platinum-refractory mucinous ovarian cancer harboring a NTRK3 gene fusion

“…This case demonstrates the promise of Entrectinib in treatment-resistant ovarian cancers harboring an NTRK gene fusion. To our knowledge, only one previous case has reported the use of Entrectinib in any category of ovarian cancer ( Endo et al, 2022 ). Entrectinib was, in that case, ineffective.…”

“…Entrectinib was, in that case, ineffective. The lack of response suggests the possibility of a false-positive genetic screening, or that NTRK rearrangements may not always be constitutively expressed ( Endo et al, 2022 ). What we believe to be the first report of successful treatment of mucinous ovarian cancer with an NTRK3 fusion with Entrectinib in our case displays the importance of next generation sequencing, especially in patients experiencing disease progression, intolerability of treatment, or tumor resistance to treatment.…”

“…One single case report from 2022 in Japan detailed a case in which Entrectinib was utilized to treat recurrent ovarian cancer with a TPM3-NTRK1 fusion. The drug was unsuccessful, thought to be due to the lack of NTRK protein expression in tumor samples ( Endo et al, 2022 ). Due to Entrectinib’s success in the treatment of other NTRK fusion-harboring cancers, it was used in our case to treat a patient with unresponsive mucinous ovarian cancer with a KANK1-NTRK3 fusion.…”

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

“…Udjus et al [199] Benjafield et al [200], Shetty et al [58], Kassan et al [201], Wetzl et al [202], Le Hiress et al [203], Pal-Ghosh et al [204], Niu, [205], Fan et al [206], Deng et al [207], Chen et al [208], Sardo et al [209], Seidel et al [210], Zhu et al [211], Omura et al [212], Hu et al [213], Castoldi et al [214], Yoshida et al [215], Palao et al [216], Kušíková et al [217], Decharatchakul et al [218], Ahmed et al [219], Merklinger et al [220], Lei et al [146], Liu et al [221], Chen et al [222], Tan et al [223], Shi et al [224], Ikonnikova et al [225], Shimodaira et al [226], Pravenec et al [227], Zhang et al [228], Shah et al [229], Cicekliyurt and Dermenci [230], Ong et al [98], Nowzari et al [163], Kim et al [231], Bonafiglia et al [232], Selle et al [233],Yoo et al [234], Kasacka et al [235], Wang et al [236], Huang et al [237], Caceres et al [238], Lei et al [239], Lu et al [240], Cui et al [241], Xiao et al [242], Hiramatsu et al [243], Oliver et al [244], Grabowski et al [245], Zhu et al [246] and Li et al [247] demonstrated that the altered expression of CASP1, EDNRA (endothelin receptor type A), F2RL1, FOXP3, TIMP4, CD74, PLK1, TGFB1, GATA6, IRF7, IRF9, BGN (biglycan), CACNA1H, FBLN2, L3MBTL4, COL1A1, POSTN (periostin), THBS4, VARS2, SOD3, ADAMTS13, FBLN5, CYGB (cytoglobin), MST1, GGT7, FGF10, CES1, CYP19A1, CD36, AQP5, ARG1, OXTR (oxytocin receptor), F11R, LEPR (leptin receptor), CDH13, DDR1, FOXO1, PAM (peptidylglycine alpha-amidating monooxygenase), S100A6, B2M, TCF4, VAMP3, GNA14, KLKB1, BDKRB1, SDC3, NFAT5, GRK3, CPXM2, EPHX2 and RCN2 are associated with hypertension. A previous study reported that CASP1 [248], EPHA5 [249], NTRK1 [250], PTN (pleiotrophin) [251], FOXP3 [252], DEF6 [253], TIMP4 [254], SOCS1 [255], CDC20 […”