Finding cancer's fingerprint

Comprehensive genomic profiling (CGP) is a way of finding the unique “fingerprint” of a cancer tumour. Using a biopsy of the tumour – with either a tissue sample, or a blood test – CGP searches for genetic mutations across a large number of cancer-related genes, identifying the ones that are known to be involved in an oncogenic process, affecting how a tumour behaves and grows. The insights from CGP help physicians refine their diagnosis, and provide prognostic information as well as predictive insights to each individual. This in turn allows physicians to match cancer-causing mutations with existing targeted therapies, and rule out unnecessary therapies. With CGP, treatments can be personalised to the unique profile of each individual’s tumour – matching the cancer’s unique “fingerprint.” Find out more.

In 2016, when Jennifer was visiting her grandchildren in Florida, she developed a cough. Upon her return home to Canada, she visited her doctor, who told her to come back if the cough didn’t go away in three weeks. The cough persisted, and her doctor referred her to an oncologist. Though Jennifer had never smoked, it turned out she had advanced lung cancer (stage IV).

“It was one of those situations, as a never-smoker, where it’s a complete shock,” said her physician, Dr. Jeffrey Rothenstein, Medical Oncologist at the Durham Regional Cancer Centre, Oshawa, Canada. Both Jennifer and he had the question that nearly every cancer patient asks: “How can this be happening and why did this happen?” Rothenstein did some initial testing, including testing for single cancer-causing genes, and Jennifer was negative. No answers.

At that point, Dr. Rothenstein brought up the option of genomic testing. He explained to Jennifer that CGP would be able to identify the specific, unique DNA mutation profile within her cancer cells, which would help him guide decisions in a treatment plan. Dr. Rothenstein had started Jennifer on chemotherapy, and she’d responded to the treatment, but both wanted to be sure they had left no stone unturned in fighting the disease. Jennifer felt relieved to have another option.

“I’m a control freak,” Jennifer said, “and I can’t control what my body is doing any more.” She agreed to have the testing. “I need to have a plan,” she told Dr. Rothenstein.

The CGP testing came back and revealed that Jennifer did have a specific mutation in her cancer that would respond to a targeted therapy. Targeted therapies treat cancer, interfering with the ability of cancer cells to grow and multiply, leading to the death of the cancer cells. While chemotherapy usually affects normal cells along with the cancer cells, targeted therapies impact only the cancer pathway that is driven by the specific genetic mutation. They are also associated with fewer adverse events than chemotherapy, and therefore a better quality of life. As researchers discover molecular pathways that drive specific cancers, drugs can be designed to block those pathways. Targeted treatments have not been discovered or developed yet for all types of cancer, but the insights from CGP helped Jennifer’s physician find the individual treatment for her.

Once Dr. Rothenstein put Jennifer on a targeted therapy, she was able to get off chemotherapy and no longer have to endure its side effects. “The treatment worked really well for her,” he said. Unfortunately, Jennifer’s cancer eventually developed resistance to this treatment, so she was subsequently switched to another targeted therapy, also identified through her genomic testing results.

Four years later, Jennifer feels fortunate. “I’m lucky to be in this age where there is a lot of emphasis put on research and development,” says Jennifer. “In addition to the wonderful medical care that I have received, I have had wonderful support from my family.”

As scientists’ understanding of the underlying causes of cancer has evolved, so have the options for CGP. CGP of biopsies can be done with a tissue sample of the tumour, or by drawing blood, since most cancer cells release DNA into the blood. Although tissue-based CGP remains the standard of care, these two types of biopsies are complementary, giving physicians options depending on the patient’s condition and personal circumstances.

For instance, liquid biopsies are useful when doing a tissue biopsy may be difficult, such as when a tumour is in a hard-to-reach location, or when there is insufficient tissue. For instance, around 20% of patients with non-small cell lung cancer (NSCLC) don’t have enough tissue available when they are diagnosed for a standard tissue-based genomic test.

For patients, liquid biopsies are simpler and minimally invasive, since they require only a single blood draw, which can be performed in an out-patient setting. Because the test is simple, it allows for quicker testing and treatment, reducing the stress patients may feel when they have to wait to schedule a biopsy, and reducing the pain or discomfort associated with some tissue biopsies, depending on their location. The simplicity of the testing also means that physicians get results faster, which is particularly important for patients with advanced cancer. Since doctors can monitor the progress of a cancer using blood samples, they may be able to skip tissue biopsy procedures. Liquid biopsies can be administered in an out-patient or even mobile setting, so they can also reduce the workload of healthcare organizations.

For patients like Jennifer, genomic testing was a game-changer in the course of her advanced disease. As it gets easier, with liquid biopsies, physicians and patients will have high-quality options to use genomic testing to get the optimal therapy, for the best outcome.

“I think we are evolving to a place where genomic profiling will be part of a routine when a patient gets diagnosed with cancer,” says Dr. Rothenstein.