Colorectal Cancer with EML4-ALK Fusion Gene Response to Alectinib: A Case Report and Review of the Literature

Hsiao, Sheng-Yen; He, Hao; Weng, Teng-Song; Lin, Cheng-Yao; Chao, Chien‐Ming; Huang, Wen-Tsung; Tsao, Chao‐Jung

doi:10.1159/000511069

Cited by 14 publications

(7 citation statements)

References 15 publications

(23 reference statements)

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“…For the treatment of CRC with TK alterations, Entrectinib is now available for CRCs with NTRK fusion. There are reports in which ALK inhibitor ceritinib and alectinib have shown efficacy in CRC with ALK fusion genes 8,32 . These reports suggest that ALK inhibitors may be effective in CRC with ALK alterations, but this requires further validation.…”

Section: Discussionmentioning

confidence: 99%

“…There are reports in which ALK inhibitor ceritinib and alectinib have shown efficacy in CRC with ALK fusion genes. 8,32 These reports suggest that ALK inhibitors may be effective in CRC with ALK alterations, but this requires further validation. At this time, it is completely unknown whether ROS-1 inhibitors and MET inhibitors are effective against CRC with ROS alteration and MET exon 14 skipping, respectively.…”

Section: Mucmentioning

confidence: 99%

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Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics

Okano,

Yamashiro,

Onagi

et al. 2023

Histopathology

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AimsTyrosine kinase (TK) alterations, such as anaplastic lymphoma kinase (ALK) fusion, neurotrophic tyrosine receptor kinase (NTRK) fusion, c‐ros oncogene 1 (ROS1) fusion and mesenchymal–epithelial transition factor (MET) exon 14 skipping, have been reported in colorectal cancers (CRC). We have previously reported CRCs with NTRK fusion among our cohort. However, their clinicopathological features have not been fully elucidated.Methods and resultsTissue microarray (TMA)‐based immunohistochemistry (IHC) was performed on 951 CRC lesions from 944 patients. IHC was evaluated as positive or negative for ALK and ROS1 and 0 to 3+ for c‐MET. For ALK and ROS1 IHC‐positive cases, RNA‐based imbalanced gene expression assays, Archer FusionPlex assays and reverse transcription–polymerase chain reaction (RT‐PCR) followed by Sanger sequencing were performed. For c‐MET IHC 3+ cases, RT‐PCR followed by Sanger sequencing were performed. ALK IHC was positive in three cases (0.2%) and all showed imbalanced ALK gene expression. The following ALK fusions were confirmed: EML4 (exon 21)::ALK (exon 20), EML4 (exon 6)::ALK (exon 19) and HMBOX1 (exon 6)::ALK (exon 20). Two showed microsatellite instability‐high/mismatch repair (MMR)‐deficient, and all were located in the right colon. ROS1 IHC was positive in one case; however, imbalanced expression and ROS1 fusion was negative. Forty‐two cases (4.4%) showed c‐MET IHC3+. MET exon 14 skipping was confirmed in nine cases. All cases were microsatellite stable/MMR‐proficient, and eight were located in the left colon and rectum.ConclusionsCRCs with these TK alterations had distinct clinicopathological features. Together with our previous study, 15 cases (1.6%) harboured targetable TK alterations (three NTRK fusion, three ALK fusion, nine MET exon 14 skipping).

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Section: Discussionmentioning

confidence: 99%

Section: Mucmentioning

confidence: 99%

Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics

Okano,

Yamashiro,

Onagi

et al. 2023

Histopathology

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“…However, the role of EML4-ALK as a therapeutic target in these non-NSCLC cancers, including gastrointestinal cancers, is not well understood. From our extensive literature search, we summarize in Table 1 the case series of patients with gastrointestinal cancer who were treated with ALK inhibitors (10)(11)(12)(13)(14)(15)(16)(17). A total of 23 patients with gastrointestinal cancer and ALK fusion were treated with ALK inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Exceptional response to alectinib for duodenal carcinoma with ALK fusion: A case report and literature review

Isaka¹,

Sasaki²,

Saito³

et al. 2023

Front. Oncol.

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Patients with advanced duodenal carcinoma usually have a poor prognosis due to limited effective chemotherapy options. The study for genotype-directed therapy in patients with duodenal carcinoma is progressing. However, no clinical data assessing the efficacy of molecularly targeted therapy are presently available. We report the case of a 64-year-old woman who was diagnosed with anaplastic lymphocyte kinase (ALK) fusion-positive advanced duodenal carcinoma. Echinoderm microtubule associated protein like-4 (EML4)-ALK rearrangement was detected by comprehensive genomic profiling after resistance to first-line chemotherapy. The patient received alectinib, an ALK inhibitor, with marked shrinkage in primary tumor and liver metastases. She is currently being treated with alectinib for 6 months or more. This is the first report of the efficacy of alectinib in a patient with duodenal carcinoma harboring ALK fusion. Additionally, this case report suggests that the practical use of next-generation sequencing may expand optimal treatment choices in rare solid tumors, including duodenal carcinoma.

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“…Like the other PCR tests, only detecting known mutations and a relatively small number of targets limit their applications to certain patients and diseases. Compared to PCR-based approaches, NGS can detect more genes simultaneously and covers more different types of alterations in genes, not only point mutations, but also insertion or deletion, amplification and microsatellite instability [ 48 ], as well as gene fusions and translocations that may be targetable in different types of cancer [ 49 , 50 , 51 , 52 ]. Now, the FDA has already approved two NGS- based liquid biopsy ctDNA testing assays, the Guardant360 CDx assay and the FoundationOne CDx assay which can sequence 55 genes and 311 genes respectively [ 53 ].…”

Section: Detection Of Therapeutically Targetable Mutations In Ctdnamentioning

confidence: 99%

Liquid Biopsy, ctDNA Diagnosis through NGS

Chen

Liu

Zheng

et al. 2021

Life

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Liquid biopsy with circulating tumor DNA (ctDNA) profiling by next-generation sequencing holds great promise to revolutionize clinical oncology. It relies on the basis that ctDNA represents the real-time status of the tumor genome which contains information of genetic alterations. Compared to tissue biopsy, liquid biopsy possesses great advantages such as a less demanding procedure, minimal invasion, ease of frequent sampling, and less sampling bias. Next-generation sequencing (NGS) methods have come to a point that both the cost and performance are suitable for clinical diagnosis. Thus, profiling ctDNA by NGS technologies is becoming more and more popular since it can be applied in the whole process of cancer diagnosis and management. Further developments of liquid biopsy ctDNA testing will be beneficial for cancer patients, paving the way for precision medicine. In conclusion, profiling ctDNA with NGS for cancer diagnosis is both biologically sound and technically convenient.

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Colorectal Cancer with EML4-ALK Fusion Gene Response to Alectinib: A Case Report and Review of the Literature

Cited by 14 publications

References 15 publications

Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics

Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics

Exceptional response to alectinib for duodenal carcinoma with ALK fusion: A case report and literature review

Liquid Biopsy, ctDNA Diagnosis through NGS

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