title: Advances in radiotherapy and targeted therapies for rectal cancer.
abstract: The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy. The stepwise implementation of intensity-modulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery, reducing treatment related toxicity. In addition, the administration of a simultaneous integrated boost offers excellent local control rates. The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches. However, distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread. The expected benefit of targeted therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals, hence hardly justifying rather modest improvements in patient outcomes. On the other hand, the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape. Both N2 neutrophils and myeloid-derived suppressor cells (MDSC) emerge as useful clinical biomarkers of poor prognosis, while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings. Therefore, integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.
authors.affiliation: Alexandra Sermeus, UZ Brussel, Vrije Universiteit Brussel, Department of Gastroenterology, B-1090 Brussels, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sermeus
authors.affiliation: Alexandra Sermeus, UZ Brussel, Vrije Universiteit Brussel, Department of Gastroenterology, B-1090 Brussels, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Leonard
authors.affiliation: Alexandra Sermeus, UZ Brussel, Vrije Universiteit Brussel, Department of Gastroenterology, B-1090 Brussels, Belgium.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Engels
authors.affiliation: Alexandra Sermeus, UZ Brussel, Vrije Universiteit Brussel, Department of Gastroenterology, B-1090 Brussels, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: De Ridder
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005544:Forecasting; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D058990:Molecular Targeted Therapy / Q000639:trends*; D057285:Precision Medicine / Q000639:trends*; D011878:Radiotherapy / Q000639:trends; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Biomarkers; Image-guided radiotherapy; Intensity-modulated radiotherapy; Myeloid-derived suppressor cells; Rectal cancer; Targeted therapies