Cancer becomes metastatic when it has spread throughout a person’s body and treating cancer at that stage becomes very challenging.
Dr. Marina Sharifi, a physician-scientist at the UW Health | Carbone Cancer Center, is working to better understand how molecular and genetic factors that drive metastatic breast and prostate cancers determine sensitivity to different treatment approaches, and develop blood tests that can help oncologists optimize their treatment approach for each patient.
“In estrogen-driven breast cancer, for example, the most common breast cancer subtype, we know that some women will be able to have their cancer controlled for many years with just an estrogen-blocking medication,” she said. “There are other women where their cancer will start to grow again in as few as three to six months, and right now, we don’t really know how to predict when a woman’s cancer is going to be slow growing or fast growing.”
Sharifi’s research involves collecting circulating cancer cells and cancer DNA from patient blood samples, studying the unique genetic factors of these samples to find reliable biomarkers, or indicators of whether a patient’s cancer will respond to specific types of treatment. Her work is currently focused on estrogen receptor positive breast cancer, where cancer growth fueled by the hormone estrogen, as well as breast and prostate cancers with mutations that turn on a cancer growth mechanism called the PI3 Kinase pathway.
Multiple FDA-approved drugs exist that can turn off those kinds of signaling pathways and inhibit cancer growth, and while they can be an effective treatment for most patients, other patients do not benefit. Sharifi recalled an instance during her oncology fellowship training where a patient’s cancer had a PI3 Kinase mutation and they began treatment with a targeted drug specifically for this type of mutation. However, she and the patient were disappointed to find it did not work.
“That was what really got me down the path of, why does this drug only work in half of patients with this mutation? The patient actually asked me, ‘Why didn’t this drug work?’ and I didn’t have a good answer,” she said.
Sharifi’s team plans to use the predictive biomarkers they identify to develop a clinical use blood test so that oncologists can make individualized treatment decisions that have the best chance of success and optimize the patient’s quality of life.
“I really don’t want my patients living with side effects (from a treatment) for three to six months and then find out the drug isn’t working or not working as well as we hoped, and we have to try something new,” she said.
Sharifi is also expanding her biomarker research to optimize selection of antibody drug conjugates to treat breast and prostate cancer patients. This treatment combines a potent anti-cancer agent with an antibody that is drawn to a specific protein expressed by cancer cells, delivering precision treatment while mitigating toxicity for healthy cells.
“So we’re starting to develop some new tests to say, ok, can we tell which of these target proteins are highest in a specific patient? And then we can use that information to pick the drug that targets that protein,” she said.