Conquering cancer by attacking disease’s genetic abnormalities
WHEN Teresa McKeown was diagnosed with breast cancer in 2006, her disease was easily treated with standard therapies. But 11 years later, the cancer returned. This time, it morphed into what’s called triple-negative disease, an aggressive and difficult-to-treat form.
“I had one therapy after another,” she said, “and failed them all.”
Within weeks of the cancer’s detection, a tumour had grown in her small intestine, making it difficult to eat, and her peritoneal cavity, the space surrounding the organs in the abdomen, began to fill with fluid - the latter a sign she had just months, perhaps only weeks, to live. “I began writing goodbye letters to my children,” said the 57-year-old McKeown of Valley Centre, California.
But then came the breakthrough. Through a clinical trial at Moores Cancer Centre at UC San Diego Health, a test designed to reveal the genetic abnormalities locked inside tumours found a large number of them in McKeown’s cancer. The results raised the possibility that Opdivo, a drug that triggers the immune system to attack cancer and which was approved to treat melanoma, might work against the metastatic breast cancer cells ravaging McKeown’s body.
McKeown started on the drug in early 2017. After two infusions, her tumour markers, substances in the blood that reflect the amount of underlying disease, dropped dramatically. Within eight weeks, imaging scans showed no sign of cancer anywhere in McKeown’s body. Today, she remains cancerfree.
McKeown and other patients like her are rare but powerful examples of why sequencing the genome of a tumour to uncover the mutant genetics housed in its DNA - a practice known as comprehensive tumour profiling - is fast becoming a cornerstone of cancer treatment. The approach enables doctors to match individuals with cancer with drugs that target specific genetic mutations or other abnormalities in their tumour, often leading to unexpected recommendations, such as using a melanoma therapy for breast cancer.
But whether such stunning outcomes should be the exception rather than the rule has become a contested issue among oncologists. As these tests become more routine - helped largely by Medicare, which now covers them - patients and cancer physicians alike are asking whether comprehensive tumour profiling heralds a new era for cancer care or simply a higher price tag. Every cancer is unique. Individual combinations of genetic changes, or mutations, distinguish one tumour from another, even when they begin in the same part of the body.
Two people with lung cancer, for example, could have tumours with notably different genetic profiles. And these mutations can shape how a tumour behaves, including whether it responds to treatment.
For this reason, doctors are increasingly interested in tumour profiling for their patients. “A tumour might have a mutation that suggests they might respond to a certain targeted therapy, including treatments that would not have been considered had the mutation not been found,” says Razelle Kurzrock, who leads the Centre for Personalised Cancer Therapy at Moores.
The bevy of treatments aimed against genetic mutations - called targeted therapies - means oncologists have a range of options to sort through for every patient.
The Food and Drug Administration has approved 31 targeted therapies, including several immunotherapies, potent new drugs that have brought patients meaningful improvements in survival. Many more are under investigation.
The sheer number of options, says David Hyman, who specialises in gynaecologic cancers at Memorial Sloan Kettering Cancer Centre in New York, means profiling tumours makes sense. “Many of these drugs work in a wider range of patients than traditional cancer drugs, but we won’t know who stands to benefit unless we look,” he says.