Somatic Profiling of the Epidermal Growth Factor Receptor Pathway in Tumors from Patients with Advanced Colorectal Cancer Treated with Chemotherapy ± Cetuximab

Smith, Christopher G.; Fisher, David J.; Claes, Bart; Maughan, T; Idziaszczyk, Shelley; Peuteman, Gilian; Harris, Richard; James, Michelle D.; Meade, Angela; Jasani, Bharat; Adams, Rachel; Kenny, Sarah; Kaplan, Richard; Lambrechts, Diether; Cheadle, Jeremy P.

doi:10.1158/1078-0432.ccr-12-2581

Cited by 93 publications

(102 citation statements)

References 26 publications

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“…DNA extraction and genotyping for mutations including V600E was performed retrospectively as previously reported. [16,18,19] ! Stata was used ( ,StataCorp).…”

Section: Introductionmentioning

confidence: 99%

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Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

et al. 2017

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“…DNA extraction and genotyping for mutations including V600E was performed retrospectively as previously reported. [16,18,19] ! Stata was used ( ,StataCorp).…”

Section: Introductionmentioning

confidence: 99%

“…In all patients progression events in patients during chemotherapy breaks led to shorter PFS (adjusted HR=1.27 [1.21-1.33], p<0.001). [19] Bmutant Table 2). …”

Section: Introductionmentioning

confidence: 99%

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

et al. 2017

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“…For instance, colorectal cancer (CRC) cell lines ordinarily used in preclinical studies often display microsatellite instability (MSI). MSI colorectal tumours are found in 10-15% patients 5 , but they show an indolent clinical behaviour and are less prevalent in more advanced stages of the disease, accounting for o5% in the metastatic setting 6,7 . Consequently, MSI cell lines do not properly recapitulate the clinical setting in which targeted agents are most commonly administered to CRC patients.…”

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confidence: 99%

The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets

et al. 2015

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The development of molecularly targeted anticancer agents relies on large panels of tumourspecific preclinical models closely recapitulating the molecular heterogeneity observed in patients. Here we describe the mutational and gene expression analyses of 151 colorectal cancer (CRC) cell lines. We find that the whole spectrum of CRC molecular and transcriptional subtypes, previously defined in patients, is represented in this cell line compendium. Transcriptional outlier analysis identifies RAS/BRAF wild-type cells, resistant to EGFR blockade, functionally and pharmacologically addicted to kinase genes including ALK, FGFR2, NTRK1/2 and RET. The same genes are present as expression outliers in CRC patient samples. Genomic rearrangements (translocations) involving the ALK and NTRK1 genes are associated with the overexpression of the corresponding proteins in CRC specimens. The approach described here can be used to pinpoint CRCs with exquisite dependencies to individual kinases for which clinically approved drugs are already available.

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“…microsatellite-stable (MSS) CRC in stage IV (13,14), and is still unclear whether this is correct or not.…”

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Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor

Fujiyoshi

Yamamoto

Takenoya

et al. 2017

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Abstract. Background: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear. Patients and MethodsColorectal cancer (CRC) is the third most commonly diagnosed cancer and frequent cause of cancer-related death worldwide (1). Specifically, the 5-year survival rate of patients with advanced CRC is less than 30%, and further advances in chemotherapy and surgical techniques are required to improve the survival rate of patients with CRC. Recently, novel molecular-targeting drugs, such as antibody to epidermal growth factor receptor (EGFR), are based on the molecular mechanism of carcinogenesis and achieve good efficacy. However, biomarkers are often required for appropriate therapy and are predicted based on the molecular mechanism of carcinogenesis.During carcinogenesis, genetic changes, including deletion, insertion and substitution of nucleotides, rearrangement and epigenetic changes are accumulated. At least two types of genetic changes are known: chromosomal instability (CIN) and microsatellite instability (MSI). CIN comprises of structural and numerical changes of chromosomes, whereas MSI comprises frequent mutations in the microsatellite area without obvious structural and numerical changes of chromosomes. It has been reported that in Western countries approximately 80% of CRCs exhibit CIN and 15% have MSI (2). MSI is caused by dysfunction of the mismatch repair system, which detects and repairs mismatches that occur during DNA replication (3, 4). CRCs with CIN and MSI demonstrate different clinicopathological features, probably because of different mechanisms of genetic changes (5).Sporadic CRC with high-frequency MSI (MSI-H) is prone to develop in the proximal colon and in older females. Pathological characteristics are associated with the presence of tumour-infiltrating lymphocytes, a Crohn's-like lymphocytic reaction and mucinous/signet ring cell differentiation (6-9). Although CRC with MSI-H is indicative of good prognosis in stage II and III disease (10-12), several reports suggest that the prognosis of CRC with MSI-H is poorer than that of 239 Τhis article is freely accessible online.

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Somatic Profiling of the Epidermal Growth Factor Receptor Pathway in Tumors from Patients with Advanced Colorectal Cancer Treated with Chemotherapy ± Cetuximab

Cited by 93 publications

References 26 publications

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets

Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor

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