Expression levels of ROS1/ALK/c-MET and therapeutic efficacy of cetuximab plus chemotherapy in advanced biliary tract cancer

Chiang, Nai‐Jung; Hsu, Chiun; Chen, Jen Shi; Tsou, Hsiao-Hui; Shen, Ying; Chao, Yee; Chen, Ming-Huang; Yeh, Ta Sen; Shan, Yan Shen; Huang, Shiu Feng; Chen, Li Tzong

doi:10.1038/srep25369

Cited by 23 publications

(28 citation statements)

References 34 publications

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“…In non‐small‐cell lung cancer, EGFR expression level is predictive of cetuximab benefit; however, for head and neck SCC and colon cancer, even EGFR expression level is not informative in determining if cetuximab will improve patient outcome . Rather, evaluation of downstream signaling components (e.g., members of PI3K pathway) or other receptor tyrosine kinases (e.g., c‐MET, ROS1, ALK) seems to be more informative in predicting efficacy of anti‐EGFR therapy . More work is needed to determine what molecular signatures are indicative of a positive response to anti‐EGFR treatments.…”

Section: Discussionmentioning

confidence: 99%

Comparative molecular profiling of HPV‐induced squamous cell carcinomas

et al. 2017

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Approximately 5% of all cancer incidences result from human papillomavirus (HPV) infection. HPV infection most commonly leads to cancers of the anogenital region or oropharynx. It is unknown whether different HPV‐mediated cancers collectively share a molecular signature and it is important to determine if there are targetable alterations common to different types of HPV‐positive tumors. We analyzed 743 p53 wild‐type samples of anal, cervical, oropharyngeal, and vulvar squamous cell carcinomas which underwent multiplatform testing at a commercial molecular profiling service. Expression of 24 proteins was measured by immunohistochemistry (IHC), mutation of 48 genes was determined by next‐generation and Sanger sequencing, and copy number alteration for six genes was determined by in situ hybridization. The four cohorts had remarkably similar molecular profiles. No gene had a statistically significant difference in mutation frequency or copy number change between the four different types of squamous cell carcinomas. The only significant differences between cohorts were frequency of ERCC1 and SPARC loss as determined by IHC. In all four cancer types, oncogene mutation and PD‐L1 expression was relatively infrequent. The most commonly mutated gene was PIK3CA, with mutations most often affecting the helical domain of the protein and accompanied by concurrent lack of PTEN expression. Loss of MGMT and RRM1 was common among the four cohorts and may be predictive of response to cytotoxic therapies not currently being used to treat these cancer types. The similar molecular profiles of the four cohorts indicate that treatment strategies may be similarly efficacious across HPV‐positive cancers.

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Section: Discussionmentioning

confidence: 99%

Comparative molecular profiling of HPV‐induced squamous cell carcinomas

et al. 2017

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“…The OS was 7 months [ 117 ]. Also, the combination of GEMOX with cetuximab increases PFS (7.3 vs. 4.9 months) and OS (14.1 vs. 9.6 months) of patients with ICC relative to GEMOX alone [ 118 ]. Moreover, the treatment of cetuximab for patients with CC and GBC showed one (20%) CR, three (60%) PR, and one (20%) SD of five evaluable patients, indicating that cetuximab may be effective chemotherapy for BTC [ 119 ].…”

Section: Egfr Inhibitors and Their Efficacy In Cholangiocarcinomamentioning

confidence: 99%

ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications

Jin

2020

JCM

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The erythroblastic leukemia viral oncogene homolog (ErBb) family consists of the receptor tyrosine kinases (RTK) epidermal growth factor receptor (EGFR; also called ERBB1), ERBB2, ERBB3, and ERBB4. This family is closely associated with the progression of cholangiocarcinoma (CC) through the regulation of cellular networks, which are enhanced during tumorigenesis, metastasis, and chemoresistance. Additionally, the constitutive activation of cellular signaling by the overexpression and somatic mutation-mediated alterations conferred by the ErBb family on cholangiocarcinoma and other cancers enhances tumor aggressiveness and chemoresistance by contributing to the tumor microenvironment. This review summarizes the recent findings on the molecular functions of the ErBb family and their mutations during the progression of cholangiocarcinoma. It also discusses the developments and applications of various devising strategies for targeting the ErBb family through different inhibitors in various stages of clinical trials, which are essential for improving targeted clinical therapies.

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“…However, there are few data regarding these alterations in biliary tract adenocarcinomas and previous studies reported contradictory results ( Table 1 of the supplementary data) [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. FIG-ROS1 fusions were detected by PCR in 8.7% cholangiocarcinomas [6] and 9.2%, biliary tract carcinomas (exclusively in extrahepatic biliary cholangiocarcinomas and gallbladder carcinomas) [ 7].…”

Section: Introductionmentioning

confidence: 99%