Molecular Subtypes and Personalized Therapy in Metastatic Colorectal Cancer

Graham, Donna M.; Coyle, Vicky M.; Kennedy, Richard D.; Wilson, Richard H.

doi:10.1007/s11888-016-0312-y

Cited by 42 publications

(30 citation statements)

References 83 publications

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“…However, the majority of patients with metastatic CRC (mCRC) experience a poor survival rate (3,4). A growing body of research has demonstrated the positive effect of molecularly targeted treatment on the survival rate of patients with mCRC, especially with the use of monoclonal antibodies against epidermal growth factor receptor (EGFR) (5,6).…”

Section: Introductionmentioning

confidence: 99%

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

et al. 2017

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Abstract. KRAS mutations serve a function in tumorigenesis of colorectal cancer (CRC) and guide the use of targeted drugs. However, the prognostic value of KRAS mutations and their subtypes remain controversial. The present study aimed to investigate the correlations between KRAS mutations and clinicopathological characteristics, and their prognostic significance in Chinese patients with metastatic CRC (mCRC). A total of 135 patients with mCRC were analyzed for KRAS mutations. Mutations in codon 12 and 13 were identified in 45 (33.3%) patients. Only 3 patients harbored a mutation of V600E. Compared with male patients, KRAS codon 12 mutations were more common in female patients (P<0.05). KRAS codon 13 mutations tended to arise in right-sided compared with left-sided colon cancer (P<0.05). Survival analysis was performed in 101 patients receiving primary tumor resection. Compared with KRAS codon 12 wild-type, codon 12 mutations were markedly correlated with a poorer survival (log-rank P= 0.002). No prognostic significance was revealed in codon 13 mutations. In univariate analysis, mortality risk was significantly increased by subtypes of G12D and G12V [hazard ratio (HR) =2.313, 95% confidence interval (CI) =1. P=0.03; HR=2.621, P=0.04, respectively]. The results of the present study suggested that codon 12 mutations, in particular G12D and G12V, predicted a negative prognosis in Chinese patients with mCRC. These findings require further confirmation via prospective studies with larger samples.

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Section: Introductionmentioning

confidence: 99%

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

et al. 2017

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“…A CRC immunhisztokémiai és/vagy PCR-vizsgálata a mikroszatellita-instabilitás szűrésére gyakorlatban van a Lynch-szindróma kizárására [44]. Emellett a többi biomarkerrel kapcsolatban is születtek különböző eredmények, melyek részben még ellentmondásosak, és egyelőre nem alkalmazhatók megbízha-tóan a rutin klinikai gyakorlatban [45]. Az utóbbi idő-ben elfogadott, miszerint az MSI-fenotípusú II-III.…”

Section: Terápiaunclassified

“…Egy 2015-ben publikált adat szerint az MSI-H-daganatok jól reagáltak "programozott halál-1-es" immunellenőrzésipont-gátló (pembrolizumab-) terápiára az MSS-daganatokkal ellentétben [47]. További vizsgálatok folynak különféle immunellenőrzésipont-inhibitorokkal szemben is ebben a betegcsoportban [45]. A Schlicker és mtsai által leírt 1.2-es altípusú CRC (melyben MSI és lymphocytainfiltráció jellemző) magas érzékenységet mutatott továbbá a glikogén-szintáz-kináz, a c-Src és a Wnt-szignál inhibitoraival szemben [48].…”

Section: Terápiaunclassified

Heterogén vastagbéldaganat: a fogazott útvonalon kialakuló, sporadikus laesiók jelentősége a klinikai gyakorlatban

et al. 2018

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A colorectalis daganatra ma már igen heterogén betegségként tekintünk, mely heterogenitást a kialakulásában szerepet játszó genetikai faktorok, molekuláris eltérések, különböző jelátviteli útvonalak, valamint mikro-és makrokörnye-zeti tényezők okoznak. A korábban ismert ,,klasszikus" adenoma-carcinoma szekvencia mellett az elmúlt évtizedben egy másik, alternatív útvonal is felismerésre került. Ezt ,,fogazott" útvonalnak nevezzük, mely az elváltozások kb. egyharmadáért felelős. Ezek a laesiók a molekuláris tulajdonságaikon felül makroszkópos és mikroszkópos képükben és progressziós hajlamukban, illetve prognózisukban is eltérnek a klasszikus útvonal daganataitól. Az alábbi összefog-laló közlemény ezen eltérések molekuláris tulajdonságait, makroszkópos és szövettani jellegzetességeit, illetve klinikai jelentőségét szemlélteti. Orv Hetil. 2018; 159(6): 206-214. Kulcsszavak: vastagbéldaganat, fogazott útvonal, polip, prognózis Colorectal cancer heterogeneity: the clinical impact of sporadic lesions arising via the serrated pathwayToday, colorectal cancer is regarded as a heterogeneous disease. Its heterogeneity is caused by genetic alterations, molecular aberrations, different developing pathways as well as by micro-and macroenviromental agents. In the last decade, beside the classic genetic model for colorectal tumuorgenesis that follows the adenoma-carcinoma sequence, an alternative pathway has been identified. This pathway is called the serrated pathway and it is responsible for approximately one third of all colorectal lesions. Beyond their dissimilar molecular characteristics, these tumours also show different macroscopic and histologic appearance. Moreover, their malignant potency and progressive ability distinguish them from tumours of the classic genetic model. The aim of this review is to summarize the molecular and pathologic features of serrated lesions and the serrated pathway to colorectal cancer and to highlight their clinical impact. Keywords

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“…Due to the emergence of personalized medicine in cancer treatment, the need for biomarkers giving accurate and actual insight in the state of the disease is rising quickly [1]. In recent years, many new targeted drugs have come to the market for treating cancer patients, and a lot more are expected in the upcoming years [2,3]. Circulating biomarkers such as CTCs, circulating proteins, and nucleic acids are expected to contain the biomarkers needed to select a suitable therapy.…”

Section: Introductionmentioning

confidence: 99%

Improving the CellSearch® system

Swennenhuis

Dalum

Zeune

et al. 2016

Expert Review of Molecular Diagnostics

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Introduction:The CellSearch ® CTC test enumerates tumor cells present in 7.5 ml blood of cancer patients. improvements, extensions and different utilities of the cellsearch system are discussed in this paper. Areas covered: This paper describes work performed with the CellSearch system, which go beyond the normal scope of the test. All results from searches with the search term 'CellSearch' from Web of Science and PubMed were categorized and discussed. Expert commentary: The CellSearch Circulating Tumor Cell test captures and identifies tumor cells in blood that are associated with poor clinical outcome. How to best use CTC in clinical practice is being explored in many clinical trials. The ability to extract information from the CTC to guide therapy will expand the potential clinical utility of CTC. ARTICLE HISTORY

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Molecular Subtypes and Personalized Therapy in Metastatic Colorectal Cancer

Cited by 42 publications

References 83 publications

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

Heterogén vastagbéldaganat: a fogazott útvonalon kialakuló, sporadikus laesiók jelentősége a klinikai gyakorlatban

Improving the CellSearch® system

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