Targeted Therapy of Colorectal Cancer Subtypes

Description

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Recent years have increased significantly our understanding of the genetic alterations that can underlie CRC, but also unraveled the molecular heterogeneity of the disease. Although a simple correlation between genetic pathways, histopathological features and clinical outcome cannot be established, the heterogeneity of CRC is also an opportunity for the development of targeted therapeutic approaches, able to treat an individual tumor with higher efficiency and less toxic side effects. One CRC subtype is characterized by high mutation rates (MSI-H), DNA methylation changes (CIMP-H), mutation in the BRAF oncogene and occurrence of serrated adenomas in the proximal colon. Other groups prevail in the distal colon and consist of either adenomatous polyps with chromosomal aberrations (CIN) and WNT pathway activation, or carry frequent KRAS mutation and metabolic deregulation, or have strong mesenchymal and infiltrative characteristics. Characterization of driver-mutation events in these CRC subgroups has led to the development of specific drugs targeting, for example, the MAPK pathway, but initial clinical trials have revealed unexpected response rates. The collection of chapters in this volume address the biology of specific CRC subtypes and how these may be targeted to improve precision therapy and clinical benefit for the patients. Front Matter ....Pages i-viii Colorectal Cancer Subtypes – The Current Portrait (Peter Jordan)....Pages 1-6 Targeting Colon Cancers with Mutated BRAF and Microsatellite Instability (Paulo Matos, Peter Jordan)....Pages 7-21 Targeting KRAS Mutant CMS3 Subtype by Metabolic Inhibitors (Oscar Aguilera, Roberto Serna-Blasco)....Pages 23-34 Targeting the PI3K Signalling as a Therapeutic Strategy in Colorectal Cancer (Maria Sofia Fernandes, João Miguel Sanches, Raquel Seruca)....Pages 35-53 Targeting PTEN in Colorectal Cancers (Larissa Kotelevets, Mark G. H. Scott, Eric Chastre)....Pages 55-73 Wnt Signalling-Targeted Therapy in the CMS2 Tumour Subtype: A New Paradigm in CRC Treatment? (Cristina Albuquerque, Lucília Pebre Pereira)....Pages 75-100 Impact of the Microenvironment on Tumour Budding in Colorectal Cancer (Laurent MC Georges, Laurine Verset, Inti Zlobec, Pieter Demetter, Olivier De Wever)....Pages 101-111 Anti-EGFR Therapy to Treat Metastatic Colorectal Cancer: Not for All (Marta Martins, André Mansinho, Raquel Cruz-Duarte, Soraia Lobo Martins, Luís Costa)....Pages 113-131 miRNAs as Modulators of EGFR Therapy in Colorectal Cancer (Diane M. Pereira, Cecília M. P. Rodrigues)....Pages 133-147 Back Matter ....Pages 149-150