Transcriptional Profiling May Improve Outcomes in Young-Onset Colorectal Cancer

A novel study is shedding light on factors that may affect treatment response in patients with young-onset colorectal cancer. Researchers uncovered differences in transcriptional metabolic profiles and other drivers of disease, as well as immune profiles, between younger and older patients with colorectal cancer. These findings were presented at the American Society of Clinical Oncology (ASCO) annual meeting.

In this exclusive MedPage Today video, study author Deepak Vadehra, DO, of the Gastrointestinal Center Roswell Park Comprehensive Cancer Center in Buffalo, New York, and co-leader of the Adolescent/Young Adult Translational Research Group, explained the study design and clinical significance of the results.

Following is a transcript of his remarks:

So our study looked at seeing differences at the metabolic level, comparing people with quote/unquote average-onset age of colorectal cancer versus early-onset colorectal cancer. And we wanted to sort of see, were there any differences at that metabolic level that potentially influence the rise in young-onset colorectal cancer?

We used a unique bioinformatic perspective and software model to sort of take two major databases — one’s called TCGA-COAD (The Cancer Genome Atlas-Colon Adenocarcinoma), one’s called ORIEN (Oncology Research Information Exchange Network) — and then we performed transcriptional analysis through a bunch of different methods. Eventually we were able to see what different types of pathways had differences in expression and dysregulation. And we focused on those that are important in the immune modulation and immune response to try and answer, “Is this helping to play a role in young-onset colorectal cancer?”

So what we found is that — in certain pathways that affect immune modulation, one is called the kynurenine pathway, and pathways that predict response to the immunotherapy drugs that we have available for treating different types of cancers — we saw that in young-onset colorectal cancer patients, those are sort of downregulated or underexpressed compared to those over 50, [in] which they’re overexpressed or upregulated.

So seeing that and knowing that overall young-onset colorectal cancer patients do worse clinically, is this a potential driver to — they just don’t respond to these types of therapies. Is that helping to drive them doing worse clinically?

Obviously we are doing more research — we’re using biospecimens that we have, tissue samples and serum samples — to try and further validate our data in real-life humans that we’ve treated at Roswell Park. And our hope is that, one, we validate our findings. And two, eventually the downstream goal is can we target anything to help improve outcomes in young-onset colorectal cancer.

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