Enormous additions to our knowledge of human biology at the molecular and genetic level have opened the door to a potential “golden age” of cancer treatment — where every tumor has a unique signature and where personalized therapies are crafted for each patient using drugs that target specific markers on cancer cells, or even reeducate the body’s immune system. Here, we highlight five innovations that promise to dramatically shift the paradigm of cancer treatment in the coming years, from targeted immunotherapies to diversification of clinical trials to the latest in radiation technology.
Genetic Testing — A Game-Changer
“Right now there are hundreds of thousands of people at high risk for cancer who don’t know it. Tens of thousands who could benefit from targeted therapies, but won’t get them,” says Stacy Gray, M.D., City of Hope’s new director of Clinical Cancer Genomics, a division focused on identifying people and families with elevated cancer risk and then helping to manage or even eliminate that risk.
Genetic testing. Or, more accurately, the lack of genetic testing. But that is changing, and it could dramatically alter the face of cancer care in the next few years.
Stacy Gray, M.D.
Ever since 2003, when scientists successfully mapped the human genome, personalized therapy based on a patient’s genetic information has become the holy grail of cancer treatment. Where once doctors depended on chemotherapy, surgery and radiation, now it is possible to analyze the DNA of a person’s tumor and use therapies designed to target the specific mutations found. In addition, by analyzing the person’s individual DNA, physicians may identify mutations that put that person at high risk for certain kinds of cancer. They then can be placed on screening and treatment protocols aimed at prevention.
Almost every day, researchers discover additional mutations that may point to cancer in the future, with many of them actionable now. “There’s an explosion in need,” says Gray, even while the data is getting more complex: “We’re seeing a much broader number of patients with mutations who don’t classically fit current models,” she explains. “We need to sort this all out.”
The challenges, Gray understands, are formidable. At stake is nothing less than tomorrow’s cancer care. “We strongly believe,” she said, “that this is the future of oncology.”
Oncologists have another new arrow in their cancer-fighting quiver. They can now look for genetic or protein abnormalities in a patient’s tumor, and match those up with immunotherapies to specifically target them.
Immunotherapies harness the power of your immune system to attack cancer cells. Some you may have heard of include CAR T cell therapy, immune checkpoint inhibitors, monoclonal antibodies, treatment vaccines, and immune system modulators. Targeted immunotherapies are showing great promise for multiple types of cancer.
CAR T cell therapy, the process of reengineering a patient’s own immune cells to attack cancer, is a true breakthrough in immunotherapy. This therapy has already received Food and Drug Administration approval to treat blood cancers, and it holds enormous promise for the treatment of solid tumors. City of Hope has one of the most comprehensive CAR T cell programs in the world, with nearly 50 clinical trials that are either ongoing or soon to open treating both cancers of the blood and immune system, as well as solid tumors. More than 600 patients have undergone CAR T cell therapy at City of Hope.
A groundbreaking drug called pembrolizumab (Keytruda), an immune checkpoint inhibitor, was designed to stop the action of an immune system-blocking protein called PD-L1 so that immune cells can destroy cancer. The concentration of PD-L1 in cancer cells can be higher than 90%, making it a highly targetable protein. The drug has been used successfully to treat melanoma and other skin cancers, as well as breast, lung, endometrial, kidney, esophageal and many other types of cancer, driving once advanced, even deadly, diseases into remission.
Finding and Treating Cancer at the Same Time
City of Hope has treated its first patients using a novel radiation machine that one day might achieve the evasive goal of delivering tumor-destroying radiation in “real time” to multiple masses. It could be a revolutionary step forward for people with advanced cancers who previously wouldn’t have been considered for such therapy.
Terence Williams, M.D., Ph.D.
The device, called the RefleXion X1, offers a broader ability to shape the radiation beamlets aimed at tumors and to account for body and organ movement, which can help doctors shape radiation dosages and exposures in ways that limit damage to surrounding tissue. It can also detect tumors anywhere in the body during the same session in which they are treated.
Two patients, each with advanced metastatic cancer, began treatment in early August 2021. One patient wasn’t a candidate for surgery, and surgery wasn’t quite enough for the other. Both are doing well after the novel radiotherapy.
The machine’s full therapeutic potential has yet to be fully explored. It awaits the results of several small trials to earn full approval from the Food and Drug Administration (FDA). That decision might come as early as 2022.
“If it works successfully, we’re talking about changing the paradigm of what we consider curable in the metastatic setting,” said Terence Williams, M.D., Ph.D., chair of the Department of Radiation Oncology.
Increasing Diversity in Clinical Trials
People of different races, ethnicities, ages and sexual orientations have varying physical, genetic and environmental factors and vulnerabilities that come into play with diseases. A medication, for example, may affect patients of different races or even ages differently. If this is not researched and tested during clinical trials, crucial information may be missed.
City of Hope scientists aim to change that. “Our clinical and research scientists are conducting research studies on health disparities within diverse communities and helping us find the best ways to address complex health issues, including diversity in clinical trials,” says Angela L. Talton, senior vice president and chief diversity, equity and inclusion officer at City of Hope.
Kimlin Ashing, Ph.D.
City of Hope scientists are studying how diverse populations have different risk factors for and are affected differently by prostate, lung, skin, breast, colon and other cancers, as well as other diseases. The effectiveness of a treatment is often related to genetic factors — yet the patients enrolled in most clinical trials are primarily white. So City of Hope is strategically accruing people of many races to studies to advance precision medicine by exploring potential racial and ethnic differences in treatment efficacy and outcomes due to genomic variation.
Kimlin Ashing, Ph.D., professor in the Division of Health Equities, said she is optimistic that City of Hope is taking a significant lead in making clinical trials more inclusive.
“City of Hope has recruited scientists with a specific interest in clinical trial diversity in their own research and secured funding for health equity research, and we are better able to harness the wealth of expertise we have here,” she said. “We’re changing the paradigm of how you do clinical studies.”
The Promise of PIPAC
City of Hope has treated its first patient with a new chemotherapy-delivery system called PIPAC, short for pressurized intraperitoneal aerosol chemotherapy. The PIPAC clinical trial at City of Hope — the first in the United States — is being led by principal investigator Thanh Dellinger, M.D., gynecologic oncology surgeon.
The advanced ovarian cancer patient had already exhausted multiple avenues of treatment before she enrolled in Dellinger’s trial. She is having excellent results with far fewer side effects than traditional chemotherapy.
Thanh Dellinger, M.D.
The patient had multiple areas of metastasis in the abdominal area. Such tumors tend to be extremely small nodules that can proliferate to such an extent that surgery becomes impossible. And IV chemotherapy has proved a poor alternative. PIPAC delivers chemo directly into the abdomen so that it actually touches these surface metastases.
The minimally invasive treatment employs a standard technique used in diagnostic laparoscopy, in which carbon dioxide gas is directly introduced into the abdomen, creating pressure that elevates the abdominal wall and creates spaces around the organs. PIPAC employs a nebulizer pen connected to a high-pressure injector to drive an aerosolized form of chemotherapy deep into the abdominal crevices. The organs bathe in this mist for half an hour, then the droplets are vacuumed out.
The procedure takes approximately 90 minutes, followed by an overnight hospital stay. Trial patients will undergo the procedure every six weeks for up to six cycles. PIPAC produces minimal side effects because it uses only 10% to 20% of the typical chemotherapy dose.
The phase I trial originally enrolled 16 patients. However, the results have been so promising, it will be expanding to 22. It is open to patients with peritoneal carcinomatosis who have failed at least one cycle of standard chemotherapy treatment.
Another arm of the trial, for colorectal cancer that has spread to the peritoneum, will be opening soon. The principal investigator is City of Hope surgical oncologist Mustafa Raoof, M.D.
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