D5 Molecular and genomic diagnosis

Topic

Molecular oncology diagnostics involve the direct reading of genomic parameters that describe a tumor's clonal evolution: identifying the driver mutations that fuel tumor proliferation—such as mutations in the gene encoding the epidermal growth factor receptor (EGFR) or other known driver genes.

Beyond these driver mutations, molecular oncology diagnostics also assess other parameters of this same clonal evolution: biomarkers predicting immunotherapy response—such as the tumor's total mutation burden, the presence of genetic instability (specifically microsatellite instability), or the expression levels of molecules used by the tumor to inhibit T-cells; defects in the tumor's DNA repair mechanisms; and resistance mutations that emerge as treatment progresses.

The information gathered through molecular oncology diagnostics transforms a generic diagnosis like "lung cancer" into one that is far more specific and actionable—for instance, "lung adenocarcinoma with a specific EGFR mutation, treatable in the first line with osimertinib"—a level of diagnostic precision that simply did not exist prior to the advent of molecular oncology diagnostics.

The systematic application of molecular oncology diagnostics was made possible by next-generation sequencing, which drastically reduced the cost and time required to analyze a tumor's entire genome: tasks that once took weeks now take days, and whereas previously only a single gene could be analyzed at a time, it is now possible to analyze comprehensive panels comprising thousands of genes simultaneously.

Thanks to these reductions in time and cost, next-generation sequencing has become the standard of care for non-small cell lung cancer, melanoma, colorectal cancer, ovarian cancer, and many other tumor types. The resulting molecular profile is no longer an additional test ordered after the treatment decision has been made; it is the very foundation upon which the decision regarding which cancer treatment to prescribe is based.

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