Dr. Austin Dosch: Why Genomic Profiling Is Essential For Colorectal Cancer Treatment Planning

Genomic profiling is increasingly central to how clinicians characterize colorectal cancer and select systemic therapies. While histopathology and immunohistochemistry remain essential, they provide a limited view of tumor biology. Next-generation sequencing (NGS) offers a complementary, more granular assessment by identifying activating mutations and broader molecular features that can directly inform treatment strategy.

“We’re limited when we look at immunohistochemistry just on certain characteristics of the tumor. Genetic testing allows us to profile activating mutations,” Dr. Austin Dosch, a colorectal cancer surgeon and oncologist at University of Miami Miller School of Medicine, notes.

Understanding this molecular layer is now routinely influencing frontline and later-line decision-making. A common example is KRAS status, which helps determine the utility of anti-EGFR therapies. “[With] something like KRAS mutations, for instance … we know certain drugs like anti-EGFR agents may not work if KRAS mutations are present,” Dr. Dosch explains.

Beyond KRAS, identification of other actionable or prognostic alterations — such as activating BRAF mutations or additional pathway-level changes — can shape sequencing of therapies and clinical trial consideration.

“Certain specific molecular profiles … will allow us to tailor treatments to those patients in the future if they do progress or relapse, give them more treatment options,” Dr. Dosch adds.

NGS also captures higher-order genomic characteristics that are not discernible on routine immunohistochemistry, including tumor mutational burden and other features associated with potential immunotherapy sensitivity.

“If patients have a high mutational burden that may, for instance, make them more susceptible to immunotherapies, that may not be something that we see on any immunohistochemistry study, but certainly is important for their potential treatment options,” Dr. Dosch explains.

Integrating NGS Findings Into Treatment Plans

The practical challenge for clinicians is less about obtaining genomic data and more about interpreting and operationalizing it. Large-panel NGS generates extensive molecular information, and its clinical value depends on integrating those findings into a coherent treatment plan.

Clinicians now have the ability to approach treatment planning in a more personalized way, Dr. Dosch explains.

This shift reflects a broader move away from uniform treatment algorithms toward biologically driven stratification. Rather than applying identical regimens across heterogeneous disease, clinicians can increasingly base decisions on predicted tumor behavior and therapeutic responsiveness.

“There’s so much that we can do for patients just by looking how their specific tumor behaves and will react to treatment rather than just treating everybody the same across the board,” Dr. Dosch adds. “And I think that’s where the major advantages lie.”

Clinical Perspective

Genomic profiling is evolving to a core component of colorectal cancer management.

By defining actionable alterations, predicting resistance to targeted agents, and identifying patients more likely to benefit from immunotherapy, NGS supports more rational therapy selection and more strategic sequencing across lines of treatment.