Identification of Clinically Relevant Molecular Subtypes in Colorectal Cancer: The Dawning of a New Era

Abstract

In recent years, a number of protein and genomic‐based biomarkers have begun to refine the prognostic information available for colorectal cancer (CRC) and predict defined patient groups that are likely to benefit from systemic treatment or targeted therapies. Of these, KRAS represents the first biomarker integrated into clinical practice for CRC. Microarray‐based gene expression profiling has been used to identify prognostic signatures and, to a lesser extent, predictive signatures in CRC. Despite these advances, a number of major challenges remain. This article, which is based on a lecture delivered as part of the 2013 Bob Pinedo Cancer Care Prize, reviews the impact of molecular biomarkers on the management of CRC, emphasizing changes that have occurred in recent years, and focuses on potential mechanisms of patient stratification and opportunities for novel therapeutic development based on enhanced biological understanding of colorectal cancer.

Accuracy of 18F-FDG PET/CT in monitoring therapeutic response and detection of loco-regional recurrence and metastatic deposits of colorectal cancer in comparison to CT

“…Ozkan et al [7] and Lee et al [24] evaluated a group of CRC patients using PET/CT in the detection of disease recurrence in postoperative patients and both studies agreed with our study in high sensitivity (97% and 95% respectively) yet disagree as regarding specificity (61% and 76% respectively) as our study has much higher specificity in the detection of the local recurrence.…”

“…More than 80% of CRCs arise from adenomatous polyps but less than 1% of adenomatous polyps which are smaller than 1 cm ever become malignant [6]. Advances in our ability to detect developing CRC has begun to refine the prognostic information available and define patient groups that are likely to benefit from systemic treatment or targeted therapies [7].…”

Imaging in Colorectal Cancer: Progress and Challenges for the Clinicians

“…More than 80% of CRCs arise from adenomatous polyps but less than 1% of adenomatous polyps smaller than 1 cm ever become malignant [ 5 ]. Advances in our ability to detect developing CRC has begun to refine the prognostic information available and define patient groups that are likely to benefit from systemic treatment or targeted therapies [ 6 ].…”

Modification of cysteine 457 in plakoglobin modulates the proliferation and migration of colorectal cancer cells by altering binding to E-cadherin/catenins

“…This makes understanding the molecular mechanisms and genetic changes associated with CRC progression crucially important for the discovery of new therapeutic targets as well as the identification of patients who are at high risk. [2] During tumor progression, cancer cells modify their stromal environment by generating a range of growth factors and proteases. [3] The tumor microenvironment is characterized by hypoxia, low pH, and nutrient deprivation, which together cause severe alterations in cell metabolism and physiology, including hypoxiareoxygenation injury, inflammatory cell activation, and the induction of oxidant-generating enzymes.…”