Cathy Smithwick, now 67, has lived with breast cancer, and then ovarian cancer, for more than 20 years with the help of targeted drugs, drugs that harness the body's immune system, chemotherapy and hormone pills.
Michelle Vacca, who recently turned 59, has had lung cancer for nearly 10 years and is doing well on an experimental drug that targets a rare tumor mutation.
Both are among a growing number of Americans living with cancer as scientists continue to unravel the biological underpinnings of the disease and develop new drugs that target a tumor's genetic signature.
The American Cancer Society estimates that 18 million Americans who have ever had cancer are alive today.
A record seven out of 10 cancer patients now survive for at least five years, up from less than half in the 1970s and 63% in the mid-1990s, when drugs designed to specifically damage cancer cells began to emerge, according to the cancer society.
Chemotherapy that kills all fast-growing cells -- still a backbone in oncology treatment -- had been the only option for most cancers.
"It's taken decades for us to really understand the biology of cancer," said Rebecca Siegel, head of surveillance research at the cancer group. She expects survival rates to continue to rise, although cancer, which becomes more common with age, will likely remain the No. 2 cause of death after heart disease.
The just-concluded meeting of the American Society of Clinical Oncology in Chicago highlighted a study showing that cancer deaths in people between the ages of 15 and 49 have dropped 25% since 1990, along with trial results for new life-extending drugs for pancreas cancer, skin cancer and blood cancers.
Cancer develops when mutations in cellular DNA cause cells to grow and divide uncontrollably. The changes can be triggered by exposure to things like tobacco or ultraviolet rays, but in a smaller number of cases the mutations are inherited.
To secure regulatory approval, a new drug needs to be safe and effective, often using measurements like tumor shrinkage rather than overall survival. Less than a third of cancer drugs approved in recent years were shown to extend life spans.
Success rates are improving in part because trials that select patients based on specific genetic markers or mutations have nearly doubled the success rate of unselected trials.
Newer options like Revolution Medicines' daraxonrasib, which targets a variant of the RAS gene that drives cancer growth, can allow patients to overcome resistance to standard treatments, said Dr. Vincent Chung, pancreas cancer specialist at City of Hope, a national cancer research and treatment organization.
"This is how you have patients that are living with cancer... if you've been on a targeted therapy, you're going to be probably more sensitive to the older chemotherapy again," he said.
Living, but with cancer
Smithwick, who worked as a management consultant in Silicon Valley until retiring after a second ovarian cancer recurrence four years ago, was diagnosed with breast cancer in 2005. Her tumor tested positive for a protein called HER2 - found in around 25% of breast cancers - and she was given Roche's Herceptin, one of the first antibody drugs designed to block a cancer-causing protein.
She was not tested for the BRCA1 gene mutation associated with cancer risk until a sister was diagnosed with breast cancer several years later.
Smithwick was diagnosed with ovarian cancer after surgery in 2010. If her cancer became resistant to a drug, other treatments were started, but she had an allergic reaction to platinum-based chemo and can no longer get that treatment.
She now takes an estrogen-targeting pill, but if her tumor gets large enough, doctors at Kaiser Permanente will do a biopsy to test for other genetic markers.
"They will test for all available markers," said Smithwick, who did a 4-mile climb in the Himalayas of Bhutan in November and will embark on a fourth trip to Kenya this summer. "Meanwhile I am living my life."
Vacca, an office manager in Orange County, California, who has never smoked, was diagnosed with lung cancer at an early stage during an unrelated chest x-ray.
After surgery, a biopsy showed a mutation known as EGFR and Vacca was treated with AstraZeneca's tyrosine kinase inhibitor Tagrisso, but the cancer came back.
Treatment with another drug caused a rash that became infected. City of Hope found that her cancer had the EGFR 20 insertion mutation, seen in only around 2% of lung cancers, and she was enrolled three years ago in a trial of a drug known as CLN-081.
"It's still working for me," Vacca said. "I don't really have any side effects... It hasn't stopped me from traveling to K-pop concerts."
Dr. Saro Armenian, director of City of Hope's survivorship program, said the center is "doubling down on research to understand the journey of cancer survivors," while acknowledging that patients can still face a dire prognosis.
Dr. Julie Gralow, ASCO's chief medical officer, said: "We're going to have to look at the full genomic profile of every cancer."
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