Published online Jan 7, 2014. doi: 10.3748/wjg.v20.i1.1
Revised: November 12, 2013
Accepted: November 28, 2013
Published online: January 7, 2014
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.
Core tip: The stepwise implementation of intensity-modulated and image-guided radiation therapy enabled us to anatomically sculpt dose delivery and prescribe a simultaneous integrated boost, thus reducing treatment related toxicity. However, distant control remains unsatisfactory and indicates an urgent need for biomarkers of tumor spread. The immune landscape of colorectal cancer is now better clarified with regard to protumor N2 neutrophils and myeloid-derived suppressor cells (MDSC) that emerge as useful prognostic biomarkers. The growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity. Therefore, integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.