Role of genomics in colorectal cancers
Advancements in genomics has paved the way for better classifications of colorectal cancers (CRC) and the use of precision therapy.
Colorectal cancer is not a single disease, but a set of molecularly distinctive diseases with the same clinical presentation, said Associate Professor Ho Gwo Fuang, clinical oncologist at the University Malaya Medical Centre. By stratifying patients into clinically relevant molecular subtypes, treatment can be more personalized. Genomics advancements has allowed for better risk stratification of early stage disease and these are carried out by gene signature profiling tools such as ColoPrint, Ocotype Dx and ColDx (now called GeneFx Colon).
There are four consensus molecular subtypes of CRCs: CSM1 to 4. CSM1 tumours are more commonly found in the proximal colon. Generally, they are poorly differentiated, of mucinous subtype and have dense lymphocytic infiltration. This indicates strong antitumoural immune response which makes good targets for immune checkpoint inhibitors. CSM 2 to 4 are usually located towards the distal part of the colon and rectum. CSM 2 and 3 tumours are immune-ignorant and CSM 4 tumours are immune-tolerant. The most common mutation pathways in CRC include APC, RAS and Wnt pathways. The last occurs in 93 percent of patients, he said.