Cholangiocarcinoma with STRN-ALK translocation treated with ALK inhibitors

Valéry, Marine; Facchinetti, Francesco; Malka, David; Ducreux, Michel; Friboulet, Luc; Hollebecque, Antoine

doi:10.1016/j.dld.2021.09.001

Cited by 6 publications

(6 citation statements)

References 10 publications

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“…A retrospective analysis evaluated the predictive significance of ALK, c-ros oncogene1 receptor tyrosine kinase (ROS1), or mesenchymal to epithelial transition (MET) aberrant expression (RAM) in advanced or metastatic biliary tract cancer patients treated with gemcitabine plus oxaliplatin with or without cetuximab, and found that all RAM-high (immunohistochemistry intensity 3+ for any markers) tumors derived from ICC patients, who had shorter OS than RAM-low (immunohistochemistry intensity <3+ for all markers) ICC patients (median OS, 5.7 vs. 11.7 months, P=0.021) ( 12 ). Sporadic cases of cholangiocarcinoma with ALK rearrangement have been recently reported ( 13 – 15 ), among which two patients were confirmed to harbor EML4-ALK rearrangement, but not treated with ALK-TKIs ( 13 , 14 ). Another case described an ICC patient with STRN-ALK rearrangement, who responded to either alectinib (a response lasting for 7 months) or lorlatinib (a response lasting for 3 months) after the failure of standard chemotherapy at the first and second lines treatment ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…Sporadic cases of cholangiocarcinoma with ALK rearrangement have been recently reported ( 13 – 15 ), among which two patients were confirmed to harbor EML4-ALK rearrangement, but not treated with ALK-TKIs ( 13 , 14 ). Another case described an ICC patient with STRN-ALK rearrangement, who responded to either alectinib (a response lasting for 7 months) or lorlatinib (a response lasting for 3 months) after the failure of standard chemotherapy at the first and second lines treatment ( 15 ). In addition, there were four phase II clinical trials (NCT02374489, NCT02638909, NCT02034981, and NCT02568267) assessing the efficacy of different TKIs (crizotinib, ceritinib, or entrectinib) in advanced solid tumors, including cholangiocarcinomas, all of which harbored ALK, ROS1, or neurotrophin receptor kinase (NTRK) rearrangements.…”

Section: Discussionmentioning

confidence: 99%

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An unresectable and metastatic intrahepatic cholangiocarcinoma with EML4-ALK rearrangement achieving partial response after first-line treatment with ensartinib: a case report

Huang,

Li,

Huang

et al. 2023

Front. Oncol.

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Systemic chemotherapies are the primary treatment options for patients with unresectable and metastatic intrahepatic cholangiocarcinoma (ICC), but the effectiveness of current systemic therapies is limited. The development of targeted-therapy has changed the treatment landscape of ICC, and comprehensive genome sequencing of advanced cholangiocarcinoma patients could be beneficial to identify potential targets to guide individualized treatment. Herein, we reported an unresectable and metastatic ICC patient who detected EML4-ALK rearrangement in peripheral blood, which was later confirmed on tissue-based testing, and achieved partial response (PR) after first-line treatment with ensartinib. This case suggests that the liquid biopsy is of clinical value for unresectable or metastatic ICC, and the discovery of rare molecular targets provides new therapeutically approaches for advanced ICC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An unresectable and metastatic intrahepatic cholangiocarcinoma with EML4-ALK rearrangement achieving partial response after first-line treatment with ensartinib: a case report

Huang,

Li,

Huang

et al. 2023

Front. Oncol.

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“…В то же время четыре случая ХК с RETтранслокациями оказались включены в клинические испытания двух препаратов из нового класса селективных RET-ингибиторов -пралсетиниба и селперкатиниба, и в 3/4 (75 %) случаев зарегистрированы частичные ответы на лечение [38,39]. Опубликованы единичные отчеты о клинических случаях опухолей билиарного тракта с ALKи ROS1-транслокациями: применение таргетных ингибиторов киназ ALK и ROS1 в этих случаях сопровождалось выраженными клиническими ответами [40][41][42].…”

Section: редкие генетические изменения в рецепторных тирозинкиназах: ...unclassified

The role of molecular diagnostics in the choice of therapy for biliary tract cancers

Mitiushkina,

Imyanitov

2024

Sib. onkol. ž.

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The aim of the study was to assess the frequency and clinical significance of various molecular genetic aberrations in biliary tract tumors and to determine the optimal methods of their testing. Material and Methods. We searched the literature sources containing information on predictive molecular markers relevant for the choice of therapy in biliary tract tumors in PubMed and eLibrary databases for the period from 2010 to 2023. data from 60 studies were included in this review. Results. Biliary tract tumors are characterized by poor prognosis and low sensitivity to major systemic therapies. Nevertheless, the emergence of new targeting drugs and prescription of therapy based on the results of molecular genetic analysis can increase the life expectancy and improve the quality of life of a significant proportion of patients. The most frequently detected clinically significant abnormalities in all biliary tract tumors include HER2 gene amplification/hyperexpression (5–20 % of cases), microsatellite instability (1–2 % of cases), BRAF V600E oncogene mutation (1–2 % of cases) and KRAS G12C oncogene mutation (about 1 % of cases). Specific targetable abnormalities unique to intrahepatic cholangiocarcinomas include aberrations in the gene encoding fibroblast growth factor receptor 2, FGFR2 (10–20 % of cases) and mutations in the gene encoding the enzyme isocitrate dehydrogenase 1, IDH1 (5–30 % of cases). Very rare clinically significant molecular markers for biliary tract tumors include translocations involving the receptor tyrosine kinase genes NTRK1-3, RET, ALK and ROS1. Mutations in the genes of the dNA double-strand break repair system by the mechanism of homologous recombination are also potentially significant for the choice of therapy. First of all, these are BRCA1/2 genes, hereditary mutations in which, according to two studies, are characteristic of 5–7 % of patients with biliary cancer. Although a significant part of the above-mentioned disorders can be detected by traditional molecular biological approaches such as PCR, IHC, FISH and Sanger sequencing, a comprehensive analysis of all molecular markers of predictive value in biliary tract tumors is difficult to perform without the help of next-generation sequencing (NGS). Conclusion. To improve treatment outcomes of patients with advanced and metastatic biliary tract cancer by individualizing drug therapy, it is necessary to perform comprehensive molecular genetic analysis of tumour tissue.

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“…Translocations involving known targetable genes, such as ALK, ROS1, RET, and NTRK1-3, were previously reported as rare targetable alterations in BTCs (mainly, in iCCA cases) [48][49][50][51][52]. We applied a panel of RT-PCR-based tests [28][29][30][31] to the iCCA cases that were not subjected to the analysis with Illumina TruSight Tumor 170 panel; however, no such rearrangements or the MET exon 14 skipping mutations, were found.…”

Section: Other Genetic Alterations Detected In Iccamentioning

confidence: 99%

Molecular Analysis of Biliary Tract Cancers with the Custom 3′ RACE-Based NGS Panel

Mitiushkina,

Tiurin,

Anuskina

et al. 2023

Diagnostics

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The technique 3’ rapid amplification of cDNA ends (3′ RACE) allows for detection of translocations with unknown gene partners located at the 3′ end of the chimeric transcript. We composed a 3′ RACE-based RNA sequencing panel for the analysis of FGFR1–4 gene rearrangements, detection of activating mutations located within FGFR1–4, IDH1/2, ERBB2 (HER2), KRAS, NRAS, BRAF, and PIK3CA genes, and measurement of the expression of ERBB2, PD-L1, and FGFR1–4 transcripts. This NGS panel was utilized for the molecular profiling of 168 biliary tract carcinomas (BTCs), including 83 intrahepatic cholangiocarcinomas (iCCAs), 44 extrahepatic cholangiocarcinomas (eCCAs), and 41 gallbladder adenocarcinomas (GBAs). The NGS failure rate was 3/168 (1.8%). iCCAs, but not other categories of BTCs, were characterized by frequent FGFR2 alterations (17/82, 20.7%) and IDH1/2 mutations (23/82, 28%). Other potentially druggable events included ERBB2 amplifications or mutations (7/165, 4.2% of all successfully analyzed BTCs) and BRAF p.V600E mutations (3/165, 1.8%). In addition to NGS, we analyzed microsatellite instability (MSI) using the standard five markers and revealed this event in 3/158 (1.9%) BTCs. There were no instances of ALK, ROS1, RET, and NTRK1–3 gene rearrangements or MET exon 14 skipping mutations. Parallel analysis of 47 iCCA samples with the Illumina TruSight Tumor 170 kit confirmed good performance of our NGS panel. In conclusion, targeted RNA sequencing coupled with the 3′ RACE technology is an efficient tool for the molecular diagnostics of BTCs.

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Cholangiocarcinoma with STRN-ALK translocation treated with ALK inhibitors

Cited by 6 publications

References 10 publications

An unresectable and metastatic intrahepatic cholangiocarcinoma with EML4-ALK rearrangement achieving partial response after first-line treatment with ensartinib: a case report

An unresectable and metastatic intrahepatic cholangiocarcinoma with EML4-ALK rearrangement achieving partial response after first-line treatment with ensartinib: a case report

The role of molecular diagnostics in the choice of therapy for biliary tract cancers

Molecular Analysis of Biliary Tract Cancers with the Custom 3′ RACE-Based NGS Panel

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