title: Emerging drugs in refractory colorectal cancer.
abstract: Colorectal cancer is the third leading cause of cancer-related deaths in the western world. Despite therapeutic advances, the prognosis of metastatic colorectal cancer patients remains poor due to intrinsic or acquired tumor drug resistance. The main mechanisms of tumor drug resistance are represented by genetic and epigenetic alterations. This leads to tumor refractoriness during treatment or disease progression following response to first-line therapy. Strategies to combat chemorefractory tumors involve the development of selective inhibitors of drug-resistant phenotypes, the epigenetic resensitization of drug-resistant cancer cells and new cytotoxic drugs devoid of cross resistance with first-line cytotoxics. The use of drug combination regimens may also increase treatment efficacy, and the exploitation of specific phenomena such as oncogenic and nononcogenic addiction or synthetic lethality represents another potential approach in combating tumor drug resistance. Clinical trials based on such strategies in mCRC patients whose tumors progressed following first-line chemotherapy are discussed herein.
authors: Section of Clinical Pharmacology & Oncology, Department of Health Sciences, University of Florence, viale Pieraccini, 6 - 50139 Florence, Italy.
authors: Stefania
authors: S
authors: Nobili
authors: Section of Clinical Pharmacology & Oncology, Department of Health Sciences, University of Florence, viale Pieraccini, 6 - 50139 Florence, Italy.
authors: Alessandro
authors: A
authors: Galletta
authors: Specialty School in Medical Oncology, University of Florence, viale Pieraccini, 6 - 50139 Florence, Italy.
authors: Marco
authors: M
authors: Brugia
authors: Department of Experimental & Clinical Medicine, University of Florence, viale Pieraccini, 6 - 50139 Florence, Italy.
authors: Renato
authors: R
authors: Tassi
authors: Specialty School in Medical Oncology, University of Florence, viale Pieraccini, 6 - 50139 Florence, Italy.
authors: Paolo
authors: P
authors: Petreni
authors: Department of Experimental & Clinical Medicine, University of Florence, viale Pieraccini, 6 - 50139 Florence, Italy.
authors: Ida
authors: I
authors: Landini
authors: Department of Experimental & Clinical Medicine, University of Florence, viale Pieraccini, 6 - 50139 Florence, Italy.
authors: Enrico
authors: E
authors: Mini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D055808:Drug Discovery / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents