Comprehensive genomic profiling as an important cancer diagnostic tool

June 22, 2022

Even as cancer diagnoses and treatments continue to make great strides, one fact remains abundantly clear. A half century of intense research shows that cancer, in all its myriad forms, remains a dangerous adversary. What was once thought of as a single, monolithic disease is now understood to be a series of genetically defined subdiseases often unique to each patient. Determining which treatment, or combination of treatments, that will be most effective for each particular patient requires precise diagnostic tools. Fortunately, clinical laboratories have a powerful tool at their disposal: comprehensive genomic profiling (CGP).

With our understanding of biology accelerating at a rapid pace, now is the right time for CGP testing. For labs, it offers the ability to test multiple genes at once, placing valuable data quickly into the hands of physicians who can create personalized treatment plans for their patients.

One test instead of many

Often, physicians seeking to provide optimal cancer care for each of their patients must manage huge data sets produced from multiple clinical and genomic test reports, each of which examines only a small number of mutations within an equally confined subset of genes. This takes precious time, potentially delaying treatment and perhaps not leading to the most optimal therapy. CGP refines and streamlines this process by using one comprehensive test panel to look for the four main types of genomic alterations triggering cancer growth: base substitutions, insertions and deletions, copy number alterations, and rearrangement of fusions. It then generates a detailed report pinpointing specific molecular alterations in a patient’s cancer and matching them with targeted therapies.

Some of the current CGP tests can assess more than 300 cancer-associated genes using a single blood or tissue sample. This not only helps patients avoid unnecessary treatments, but also the discomfort and inconvenience of repeated biopsies. This is CGP’s strongest plus. Rather than requiring multiple tissue samples to perform different single-gene tests, one can get much more information from a single patient sample. Biopsies are an invasive procedure, so being able to look at many different things using only one test is a big advantage. And it makes the best use of a very precious resource—the patient’s sample.

A treasure trove of data

The enormous amount of data that is captured by each CGP test allows physicians to go beyond simply treating the individual patient. CGP can build up the information base around different types of genomic alterations, as the biology underlying many cancers is still imperfectly understood. For instance, how do these mutations relate to the cancer itself, its progression, the treatment response to the cancer, or its resistance to various treatments? Clinical research, to which CGP data could greatly contribute, further builds our understanding of the biology around cancer. It powers new ideas around drug development and targeted therapies that go after different molecularly defined subtypes of the disease in new ways.

CGP also helps researchers determine whether treatments that work on one type of cancer might also work on others. For instance, in theory, CGP results might find the same genetic alteration in two different forms of cancer. In such a case, the specific therapies applied successfully to one ailment may work for another but would need to be tested in the context of a clinical trial.

It is important for laboratories and laboratorians to understand the value to the physician, the patient, and the healthcare system in being able to provide a comprehensive genetic profile of an individual patient’s sample. It can strongly influence care management by driving how physicians develop an understanding of their patients and how they arrive at treatment decisions with them. This trove of information, when collated with thousands of other individual data sets, could also be a boon for clinical research.

Only the beginning

As technology improves, laboratories will be able to look at more and more genes using a single test and interrogate them for alterations. That data can be aligned and mapped to a reference genome in order to determine how the cancerous sample deviates from it. The amount of information thus gleaned from CGP assays will continue to grow, increasing the types of alterations that are examined, identified, and reported to physicians. There are currently comprehensive genomic profiling tests available that can cover several hundred genes, out of the approximately 30,000 total genes in human DNA across 3 billion base pairs.

CGP will likely become a fixture in laboratories, and its capabilities will certainly improve. Inevitably someone, somewhere will find a gene that is highly important in, let’s say, lung cancer, and it is not in the set of genes the test looks at today. Consequently, a new panel will be developed that includes the new genes we have learned are important. That is why we do clinical research around cancer—to learn what is driving it and its resistance to therapies. We want to learn about new genes and mutations and make sure we capture those in the next version of the comprehensive genomic profiling test.

This creates another necessity—collating and packaging this vital information so that it can be easily used by physicians to make treatment decisions. As we get better about doing more on the sequencing side, we must get better at enabling laboratories to work within efficient time frames. And we must be able to provide the software and bioinformatics tools that enable all that information to be delivered to physicians in a way that allows them to act on it in a timely manner.

Modern science knows that each case of cancer is unique, with its own mysteries to solve. Deployed correctly, CGP can go a long way toward expediting highly individualized, highly effective treatments tailored to particular cases. First and foremost, more tests can be done with fewer tissue samples, minimizing patient discomfort. In addition, laboratories can glean vastly more data from that sample and present it in a ready-to-use manner that helps physicians expedite treatment selections. Also, the volumes of data gleaned from CGPs could help advance cancer research. It is important for clinical laboratories to enable an understanding of a particular patient’s cancer at the molecular level. It is also a key step toward truly personalized medicine. 

Robert Loberg, PhD is the Vice President and Lifecycle leader, Oncology and Genetics at Roche Diagnostics where he oversees development and commercialization of the next generation sequencing assays and oncology PCR portfolio of products.