Background
- Colorectal cancer (CRC) is a heterogeneous disease with different genetic alterations and clinical behavior
- CRC was recently classified into four consensus molecular subtypes (CMSs) with distinguishing features1
- CMS 1-4 tumors have different carcinogenic pathways and genomic patterns
- Recent retrospective analysis of CALGB 80405 showed that left-sided colon tumors respond differently to biologics compared to right-sided colon tumors1, likely due to molecular differences
- In the CALGB 80405 analysis, rectal cancers were included as part of the “left-sided” tumors
- However molecular variations between rectal and left-sided colon tumors are not well defined
Objective
- To identify the molecular variations among left-sided CRC tumors:
- Rectal cancers
- Sigmoid colon cancers
- Descending colon cancers (plus splenic flexure)
Methods
- Retrospective analysis of 1,730 CRC tumors that were profiled by Caris Life Sciences between 2009 and 2016 was performed
- All samples were independently reviewed by at least one pathologist, in addition to the local pathologist
- Only primary tumors were included in the current analysis
- Tumors without clearly defined origins were excluded
- Chi-square test was used for comparison between groups (IBM SPSS Statistics, Version 23) and significance was defined as p < 0.05
Conclusions
- Rectal cancers have molecular features that are different from left-sided colon tumors
- Clinical trials should stratify patients based on the location of the primary tumor (right vs. left) as well as molecular features
- Better understanding of disease biology may help to identify therapeutic targets and advance precision medicine