. "CZ - \u010Cesk\u00E1 republika" . "Z(MZ0MOU2005)" . "The monoclonal antibodies panitumumab and cetuximab that target the epidermal growth factor receptor are effective in approximately 10% and 20% of EGFR expressing, chemotherapy resistant metastatic colorectal cancer patients in monotherapy and in combination with chemotherapy, respectively. The evidence that EGFR expression by immunohistochemistry does not predict clinical outcome in EGFR targeted treatment has led to an intensive search for additional predicitive biomarkers. Oncogenic activation of signalling pathways downstream of the EGFR, such as mutation of KRAS, BRAF, or PIK3CA oncogenes, or inactivation of the PTEN tumor supressor gene is central to the progression of colorectal cancer. Tumor KRAS mutation, which may be present in 35%\u201345% of patients with colorectal cancer, is now recognized as an important predictive marker of resistance to cetuximab or panitumumab treatment and is also widely used in clinical practice. Among tumors carrying wild-type KRAS, mutations of BRAF or PIK3CA or loss of PTEN expression may be associated with resistance to the anti-EGFR monoclonal antibody treatment. On the other hand, EGFR ligands overexpression detected in tumor tissue is a promising positive predictive marker. There are also some initial observations that gene expression profiling could also contribute to clinical decision-making about the cetuximab and panitumumab treatments. These observations require further validation in prospective clinical trials before incorporation into clinical practice."@en . . "RIV/00209805:_____/11:#0000210!RIV12-MZ0-00209805" . . . "Berkovcov\u00E1, Jitka" . . . "http://www.prolekare.cz/en/czecho-slovak-pathology-article/mollecular-predictive-markers-of-egfr-targeted-therapy-in-metastatic-colorectal-cancer-37213?search=Fabian" . "Molekul\u00E1rn\u00ED prediktory c\u00EDlen\u00E9 anti-EGFR terapie u metastatick\u00E9ho kolorekt\u00E1ln\u00EDho karcinomu" . "EGFR; targeted therapy; prediction; colorectal carcinoma"@en . . "4" . . "2"^^ . . "Mollecular predictive markers of EGFR-targeted therapy in metastatic colorectal cancer"@en . . . "Mollecular predictive markers of EGFR-targeted therapy in metastatic colorectal cancer"@en . "Molekul\u00E1rn\u00ED prediktory c\u00EDlen\u00E9 anti-EGFR terapie u metastatick\u00E9ho kolorekt\u00E1ln\u00EDho karcinomu"@cs . . "\u010Cesko-slovensk\u00E1 patologie" . "RIV/00209805:_____/11:#0000210" . "5"^^ . "2"^^ . . "Terapie monoklon\u00E1ln\u00EDmi anti-EGFR protil\u00E1tkami cetuximab a panitumumab je \u00FA\u010Dinn\u00E1 u zhruba 10 % pacient\u016F s metastatick\u00FDm EGFR exprimuj\u00EDc\u00EDm kolorekt\u00E1ln\u00EDm karcinomem v monoterapii a zhruba u 20 % pacient\u016F p\u0159i kombinovan\u00E9 l\u00E9\u010Db\u011B s chemoterapi\u00ED. Prediktivn\u00ED hodnota imunohistochemick\u00E9ho vy\u0161et\u0159en\u00ED exprese EGFR nebyla prok\u00E1z\u00E1na, tak\u017Ee se intenzivn\u011B hledaj\u00ED nov\u00E9 prediktivn\u00ED biomarkery. V progresi kolorekt\u00E1ln\u00EDho karcinomu hraj\u00ED \u00FAst\u0159edn\u00ED roli patologick\u00E9 aktivace sign\u00E1ln\u00EDch drah asociovan\u00FDch s EGFR, ke kter\u00FDm mohou v\u00E9st aktivuj\u00EDc\u00ED mutace gen\u016F KRAS, BRAF, PIK3CA \u010Di inaktivace tumor supresorov\u00E9ho genu PTEN. V sou\u010Dasnosti jsou jako d\u016Fle\u017Eit\u00FD prediktor rezistence k terapii cetuximabem a panitumumabem uzn\u00E1van\u00E9 mutace KRAS prokazateln\u00E9 u 35\u201345 % kolorekt\u00E1ln\u00EDch karcinom\u016F. Detekce mutac\u00ED KRAS jsou tak\u00E9 v klinick\u00E9 praxi pou\u017E\u00EDv\u00E1ny. U n\u00E1dor\u016F, kter\u00E9 nemaj\u00ED mutovan\u00FD gen KRAS, m\u016F\u017Ee b\u00FDt rezistence k anti-EGFR c\u00EDlen\u00E9 terapii spojena s mutacemi v genech BRAF, PIK3CA \u010Di se ztr\u00E1tou exprese proteinu PTEN. Na druhou stranu pozitivn\u00EDm prediktorem se jev\u00ED nadm\u011Brn\u00E1 exprese ligand\u016F EGFR v n\u00E1dorov\u00E9 tk\u00E1ni. Rovn\u011B\u017E profilov\u00E1n\u00ED genov\u00E9 exprese by podle prvn\u00EDch v\u00FDsledk\u016F mohlo p\u0159isp\u011Bt k rozhodov\u00E1n\u00ED o indikaci l\u00E9\u010Dby cetuximabem \u010Di panitumumabem. Tato pozorov\u00E1n\u00ED si ov\u0161em p\u0159ed zaveden\u00EDm do klinick\u00E9 praxe vy\u017Eaduj\u00ED dal\u0161\u00ED validaci v podm\u00EDnk\u00E1ch prospektivn\u00EDch klinick\u00FDch studi\u00ED."@cs . . "0009-0611" . . "Fabian, Pavel" . . "213528" . "Molekul\u00E1rn\u00ED prediktory c\u00EDlen\u00E9 anti-EGFR terapie u metastatick\u00E9ho kolorekt\u00E1ln\u00EDho karcinomu"@cs . "Molekul\u00E1rn\u00ED prediktory c\u00EDlen\u00E9 anti-EGFR terapie u metastatick\u00E9ho kolorekt\u00E1ln\u00EDho karcinomu" . "Terapie monoklon\u00E1ln\u00EDmi anti-EGFR protil\u00E1tkami cetuximab a panitumumab je \u00FA\u010Dinn\u00E1 u zhruba 10 % pacient\u016F s metastatick\u00FDm EGFR exprimuj\u00EDc\u00EDm kolorekt\u00E1ln\u00EDm karcinomem v monoterapii a zhruba u 20 % pacient\u016F p\u0159i kombinovan\u00E9 l\u00E9\u010Db\u011B s chemoterapi\u00ED. Prediktivn\u00ED hodnota imunohistochemick\u00E9ho vy\u0161et\u0159en\u00ED exprese EGFR nebyla prok\u00E1z\u00E1na, tak\u017Ee se intenzivn\u011B hledaj\u00ED nov\u00E9 prediktivn\u00ED biomarkery. V progresi kolorekt\u00E1ln\u00EDho karcinomu hraj\u00ED \u00FAst\u0159edn\u00ED roli patologick\u00E9 aktivace sign\u00E1ln\u00EDch drah asociovan\u00FDch s EGFR, ke kter\u00FDm mohou v\u00E9st aktivuj\u00EDc\u00ED mutace gen\u016F KRAS, BRAF, PIK3CA \u010Di inaktivace tumor supresorov\u00E9ho genu PTEN. V sou\u010Dasnosti jsou jako d\u016Fle\u017Eit\u00FD prediktor rezistence k terapii cetuximabem a panitumumabem uzn\u00E1van\u00E9 mutace KRAS prokazateln\u00E9 u 35\u201345 % kolorekt\u00E1ln\u00EDch karcinom\u016F. Detekce mutac\u00ED KRAS jsou tak\u00E9 v klinick\u00E9 praxi pou\u017E\u00EDv\u00E1ny. U n\u00E1dor\u016F, kter\u00E9 nemaj\u00ED mutovan\u00FD gen KRAS, m\u016F\u017Ee b\u00FDt rezistence k anti-EGFR c\u00EDlen\u00E9 terapii spojena s mutacemi v genech BRAF, PIK3CA \u010Di se ztr\u00E1tou exprese proteinu PTEN. Na druhou stranu pozitivn\u00EDm prediktorem se jev\u00ED nadm\u011Brn\u00E1 exprese ligand\u016F EGFR v n\u00E1dorov\u00E9 tk\u00E1ni. Rovn\u011B\u017E profilov\u00E1n\u00ED genov\u00E9 exprese by podle prvn\u00EDch v\u00FDsledk\u016F mohlo p\u0159isp\u011Bt k rozhodov\u00E1n\u00ED o indikaci l\u00E9\u010Dby cetuximabem \u010Di panitumumabem. Tato pozorov\u00E1n\u00ED si ov\u0161em p\u0159ed zaveden\u00EDm do klinick\u00E9 praxe vy\u017Eaduj\u00ED dal\u0161\u00ED validaci v podm\u00EDnk\u00E1ch prospektivn\u00EDch klinick\u00FDch studi\u00ED." . . "[242B9ABE969F]" . "47" . .