New therapies offer hope to cancer patients. Immunotherapy, targeted molecular treatments are cutting edge. Sacramento Bee June 20th UC Davis cancer center is trying new approaches based on genetic mutations. Mice with no immune systems are used to grow tumors, test treatments
Gale Kilgore, a retired medical librarian in Amador County, went to the doctor two years ago for what she suspected was a urinary tract infection. She learned she had bladder cancer.
Doctors at Sutter Amador Hospital removed the tumor from her bladder, only to discover the cancer had spread to surrounding muscle. A subsequent round of chemotherapy at Sacramento’s UC Davis Medical Center failed to stop the disease. Surgeons removed the bladder, but the malignancy remained, eventually growing into an inoperable, fist-sized mass in her abdomen.
The spreading cancer – and a declining number of treatment options – spelled bad news for Kilgore, who was diagnosed with Stage 4 bladder cancer. Typically, less than 35 percent of patients with that diagnosis live beyond five years.
But through UC Davis, Kilgore has been able to take advantage of one of the latest advances in cancer research. The treatment has changed her outlook on fighting the disease.
Scientists at UC Davis and the Jackson Laboratory, a Maine-based medical research firm with its West Coast facilities in Sacramento, took samples of Kilgore’s tumor and grafted them onto mice that had been genetically altered to have almost no immune systems. The mice, which grew tumors identical to Kilgore’s, were given different combinations of chemotherapy drugs. After one combination successfully shrunk a mouse’s tumor, those drugs were given to Kilgore. The treatment shrunk her abdominal mass until it was nearly invisible on a CT scan in April.
“Two years ago, there wasn’t a whole lot of hope out there,” Kilgore said from her home in Pine Grove, where she lives with her husband of 58 years, Jim Kilgore. “Now I feel positive about what’s going on.”
The mouse research is one of a number of cutting-edge anti-cancer efforts happening across the Sacramento region. They mirror a worldwide trend in advances based on research into the genetic mutations that cause cancer. Treatments that target specific mutations linked to tumor growth, as well as research into immunotherapy, which uses the body’s immune system to identify cancer cells as invaders and destroy them, offer hope to cancer sufferers and their families for more effective and personalized treatments.
The reason for the explosion in cancer therapies is we can now find these (molecular abnormalities and treat them). Ralph de Vere White, director of the UC Davis Comprehensive Cancer Center
In Kilgore’s case, that meant treating her with a combination of drugs – gemcitabine and cisplatin, said her UC Davis doctor, Chong-Xian Pan.
Cisplatin, a platinum-based drug that interferes with cancer growth, hadn’t worked for Kilgore in combination with other drugs; it had only made her feel ill. However, when paired with gemcitabine, another drug that interferes with the division of cancer cells, it dramatically shrunk her abdominal tumor, just as it had with the test mouse.
“It was very new,” Pan said. “Nobody had ever had a patient and mouse respond in this same way before.”
Last week, Kilgore, 77, rested in her quiet, tidy home, surrounded by pine trees and rhododendrons in the Sierra Nevada foothills. Her energy level isn’t what it used to be before the cancer, when she golfed twice a week and weighed 50 pounds more.
She is scheduled to return to UC Davis later this month to see if her tumor has grown. With a slight smile, she said she is hoping that she and the lab mouse, which she calls “my Gale mouse,” continue to respond to treatment.
“I hope that Gale mouse is still alive,” Kilgore said.
Until recently, cancer treatment had more of a one-size-fits-all-approach. Not anymore.
As part of its mission, Jackson Laboratory is compiling a “library” of hundreds of tumors grown in mice that can be used by researchers to see how cancers with specific genetic traits respond to different treatments. Doctors dealing with a patient who has a tumor with a similar genetic profile then can see what treatments worked before and avoid those less likely to succeed.
“These mouse models have a tremendous potential to change the way we select drugs for patients,” said Susie Airhart, senior director for strategic opportunities and product development at Jackson.
Another way the laboratory’s immune-deficient mice can be used for research is by injecting them with human immune cells, creating a kind of surrogate in which people’s immune response to cancer can be studied, Airhart said. The process can help develop immunotherapy treatments.
Once a fringe science, immunotherapy now is stirring excitement among leading cancer scientists who see it as a way to eradicate some forms of cancer. With other treatments, such as chemotherapy, cancer can quickly mutate and become drug resistant. The body’s natural defenses could offer a longer-term solution or even a permanent cure, some experts believe.
“Immunotherapy is the most promising field at this time,” said Deepti Behl, Sutter Health’s medical director for thoracic oncology in the Sacramento-Sierra region. Sutter, a health care giant based in Sacramento, is participating in clinical trials of immune enhancing drugs for lung and skin cancer, sometimes coupled with more traditional radiation and chemotherapy.
It was very new. Nobody had ever had a patient and mouse respond in this same way before.
UC Davis Dr. Chong-Xian Pan
One of cancer’s more sinister trademarks is its ability to hide from the body’s immune system and grow unchecked, Behl said. Some drugs being tested could reveal a tumor’s invasive nature to the immune system’s killer T cells.
“The tumor makes itself a cloak,” she said. “These drugs target proteins on the tumor and basically unmask it so the T cells can recognize the tumor and kill it.”
UC Davis cancer researchers, meanwhile, are conducting a study to see whether tumors fragmented by beams of radiation can provoke the immune system to recognize the cancer as a foreign invader and attack it.
With targeted molecular therapy, another leading-edge approach to cancer treatment being tested at UC Davis and other major cancer centers, doctors look for mutations in patients’ genes that drive uncontrolled cell growth or suppress the body’s natural mechanisms to stop it. They respond with chemicals that zero in on the abnormalities and halt cell division or kill the cells.
Recent studies, for instance, have identified common genetic mutations in men with prostate cancer that has spread to other parts of the body, the most deadly form of the disease. The findings could lead to more targeted treatments, including with existing drugs, an international team of researchers reported in May in the scientific journal Cell.
Such therapies are possible because of today’s relatively cheap and fast sequencing of human genes, experts said. The first sequencing of the human genome took 10 years, from 1990 to 2000, and cost $3 billion. Today, it can be done in a matter of days and costs $3,000 or less. Targeted molecular treatments have emerged since the genome was first sequenced.
“The reason for the explosion in cancer therapies is we can now find these (molecular abnormalities and treat them),” said Ralph de Vere White, director of the UC Davis Comprehensive Cancer Center.
UC Davis recently partnered with a molecular-information firm called Foundation Medicine to analyze a patient’s tumor biopsies for 369 abnormalities that can drive cancer and may be treatable. The tests cost $5,000 to $6,000 each, de Vere White said.
The benefit of targeted molecular therapies, researchers said, is that they are specific and effective. The downside is that they don’t typically last for more than three to six months before cancer mutates and re-emerges. The mouse models, however, let researchers look ahead for treatments that can be useful once another has become ineffective.
Golf course beckons
The fact that the effects of gemcitabine and cisplatin may not last is on Kilgore’s mind as she prepares to return this month to UC Davis for another scan.
“Is (the cancer) going to grow June 30 or grow in 30 years?” she said.
A stoic patient, Kilgore said the “initial diagnosis was pretty traumatic.” Doctors said her light smoking, which she quit 45 years ago, might have been to blame.
Kilgore, who was once robust and athletic at 5-feet-9-inches tall, said her energy remains low two months after her treatment. Her husband does much of the shopping and housework and helps take care of her. Her friends, children and nine grandchildren have been a terrific support group, she said.
But Kilgore said she still hopes to be more of the active person she was before cancer struck.
One of her few activities, she said – in addition to watching TV, surfing the Internet on her iPad and playing dominoes with her husband – is weaving intricate baskets from the pine needles she finds around her house and on the golf course where she used to be a regular.
“I want to go play golf. I’m not a sit-still person,” she said. “The hardest part of this is graciously accepting inactivity.”