title: Methods of selecting combination therapy for colorectal cancer patients: a patent evaluation of US20160025730A1.
abstract: Colorectal cancer (CRC) is the fourth most common cancer worldwide. Targeted therapy drugs (TTDs) are a valid treatment, epithelial growth factor receptor (EGFR) inhibitors being one of the most commonly used for CRC patients. However, this treatment is only useful for patients with wild-type KRAS (wtKRAS) and is effective only on about 40 to 60% of this subset due to the high plasticity of ErbB network. Areas covered: The invention proposes the use of ErbB protein levels and ErbB receptor dimer formation as biomarkers for selecting, predicting and monitoring CRC patients showing sensitivity to the action of EGFR inhibitors to benefit from the combination therapy of EGFR and HER2 inhibitors. The in vitro data on Lim1215 cells suggest the over-activation of HER3 signaling pathway in response to the use of EGFR inhibitors on monotherapy; the use of HER2 or HER3 or MEK inhibitors in combination with EGFR inhibitors reversed this activation. Expert opinion: To assess the clinical applicability of this invention, further studies are needed since the conclusions are derived solely based on the data obtained from only one CRC cell line (Lim1215). Furthermore, other biofactors/mutations should be considered to assure the potential benefits of the combination therapies proposed.
authors.affiliation: a University of Navarra, Faculty of Pharmacy and Nutrition, Department of Organic and Pharmaceutical Chemistry , Campus Universitario , Pamplona , Spain.|b IdiSNA, Instituto de Investigación Sanitaria de Navarra , Pamplona , Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Plano
authors.affiliation: a University of Navarra, Faculty of Pharmacy and Nutrition, Department of Organic and Pharmaceutical Chemistry , Campus Universitario , Pamplona , Spain.|b IdiSNA, Instituto de Investigación Sanitaria de Navarra , Pamplona , Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Alcolea
authors.affiliation: a University of Navarra, Faculty of Pharmacy and Nutrition, Department of Organic and Pharmaceutical Chemistry , Campus Universitario , Pamplona , Spain.|b IdiSNA, Instituto de Investigación Sanitaria de Navarra , Pamplona , Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
authors.affiliation: c Department of Pharmacology , Penn State Cancer Institute , Hershey , PA , USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sharma
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D010330:Patents as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors
chemical_list: D066246:ErbB Receptors; D020929:Mitogen-Activated Protein Kinase Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3
keywords: Biomarkers; EGFR inhibitors; colorectal cancer; combination therapy; monoclonal antibodies