Metastatic colorectal cancer (mCRC) patients carrying KRAS mutated tumors do not benefit from epidermal growth factor receptor (EGFR)-targeted cetuximab- or panitumumab-based therapies. Indeed, the mutational status of KRAS is currently a validated predictive biomarker employed to select mCRC patients for EGFR targeted drugs. When patients fail standard 5-fluorouracil-oxaliplatin- irinotecan- and bevacizumab-based therapies, EGFR-targeted salvage therapy can be prescribed only for those individuals with KRAS wild-type cancer. Thus, clinicians are now facing the urgent issue of better understanding the biology of KRAS mutant disease, in order to devise novel effective therapies in such defined genetic setting. In addition to KRAS, recent data point out that BRAF and PIK3CA exon 20 mutations hamper response to EGFR-targeted treatment in mCRC, potentially excluding from treatment also patients with these molecular alterations in their tumor. This review will focus on current knowledge regarding the molecular landscape of mCRC including and beyond KRAS, and will summarize novel rationally-developed combinatorial regimens that are being evaluated in early clinical trials.
Therapeutic implications of resistance to molecular therapies in metastatic colorectal cancer / A. Sartore-Bianchi, K. Bencardino, A. Cassingena, F. Venturini, C. Funaioli, T. Cipani, A. Amatu, L. Pietrogiovanna, R. Schiavo, F. Di Nicolantonio, S. Artale, A. Bardelli, S. Siena. - In: CANCER TREATMENT REVIEWS. - ISSN 0305-7372. - 36:suppl. 3(2010), pp. S1-S5.
|Titolo:||Therapeutic implications of resistance to molecular therapies in metastatic colorectal cancer|
SARTORE BIANCHI, ANDREA (Corresponding)
|Parole Chiave:||Colorectal cancer; EGFR; KRAS; Monoclonal antibodies; Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Class I Phosphatidylinositol 3-Kinases; Colorectal Neoplasms; Disease Models, Animal; Drug Resistance, Neoplasm; Humans; Membrane Proteins; Mutation; Neoplasm Metastasis; PTEN Phosphohydrolase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Receptor, Epidermal Growth Factor; Receptors, Cell Surface; Salvage Therapy; Xenograft Model Antitumor Assays; ras Proteins; Oncology; Radiology, Nuclear Medicine and Imaging|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S0305-7372(10)70012-8|
|Appare nelle tipologie:||01 - Articolo su periodico|