Chapters authored
Genetic and Serological Markers in Identifying Unclassified Colitis
In 5–15% of the patients with inflammatory bowel disease (IBD) limited to the colon, it is difficult to distinguish histologically between ulcerative and Crohn’s colitis. This is described as unclassified colitis. Distinguishing between the two is important in terms of prognosis, since patients with Crohn’s disease (CD) have a higher risk of strictures and fistulae, which may predict a more severe disease course, as well as an increased risk for surgery. In addition, colectomy may be curative in ulcerative colitis patients not responding to medical therapy, while Crohn’s patients undergoing colectomy can have relapses in other areas of the bowel and, therefore, need to be followed-up. In inflammatory bowel disease, intestinal inflammation is believed to occur secondary to an altered immune response in a genetically susceptible host. Genetic and serological markers (antibodies) may have a role in identifying unclassified colitis. Anti-Saccharomyces cerevisiae antibody (ASCA) and anti-neutrophil cytoplasmic antibodies (pANCA) have the highest sensitivity in distinguishing ulcerative from Crohn’s colitis. Nucleotide oligomerization domain 2 (NOD2) and autophagy-related 16-like 1 (ATG16L1) polymorphisms are strongly associated with Crohn’s disease, while epithelial barrier genes are significantly associated with ulcerative colitis. This chapter describes which gene polymorphisms and serological markers may be used to distinguish between ulcerative colitis and Crohn’s disease in patients with histologically unclassified colitis.
Part of the book: New Insights into Inflammatory Bowel Disease
Acquired and Intrinsic Resistance to Colorectal Cancer Treatment
First line therapy for colorectal cancer (CRC) is usually fluoropyrimidine monotherapy and oxaliplatin, or irinotecan-based therapy. Additionally, targeted therapies such as bevacizumab, aflibercept, ramucirumab, regorafenib, cetuximab and panitumumab are indicated in combination with chemotherapy in metastatic CRC. Resistance of CRC to treatment is the principal rationale for treatment failure. Resistance can be intrinsic (primary resistance) or acquired (secondary resistance). Here, we discuss the classical model of resistance, which focuses primarily on mechanisms involving alterations in drug metabolism, increased drug efflux, secondary mutations in drug targets, inactivation of apoptotic pathways, p53 and DNA damage repair. Other resistance mechanisms, including the Warburg effect, cancer stem cells, intra-tumor heterogeneity and pharmacoepigenomic mechanisms will also be discussed. We conclude the chapter with a systems medicine approach to predict response to treatment for the discovery and validation of predictive biomarkers that are urgently needed.
Part of the book: Colorectal Cancer