It’s good to have friends in high places, and men with prostate cancer have a knowledgeable and powerful advocate working for them: Karen Knudsen, Ph.D., M.B.A., a PCF-funded investigator who in 2021 became the first woman, and the first basic science researcher, to be named CEO of the American Cancer Society (ACS) and its advocacy affiliate, the ACS Cancer Action Network (ACS CAN).
Knudsen formerly was executive vice president of Oncology Services and enterprise director for the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia – where, among other things, she more than doubled the institution’s NCI research funding and opened the first men’s genetic risk clinic in the U.S. “I thought I had my ultimate dream job at Jefferson Health,” she says. “It was fulfilling and I loved it.”
At Jefferson Health, where she still retains her professorship, “We served a very dense, heterogeneous population with high cancer risk and high cancer mortality.” And Knudsen realized something: “At the end of the day, it’s going to take research and advocacy.” The plain truth, she adds, is that “the burden of cancer in this country is unacceptably high,” and the solution is not just research, and not just support, and not just better access to care, but all of the above.
PARP Discovery
Knudsen’s roots are in basic science, and her contributions continue to help men with prostate cancer. Ten years ago, Knudsen’s group discovered that a gene called PARP1 is a driver of prostate cancer, and that PARP inhibitors may have promise as treatments. Next, Knudsen and a PCF-funded team including UCSF radiation oncologist Felix Feng, M.D., and UK scientist Johann De Bono, M.D., Ph.D., achieved a major milestone: they proved that drugs called PARP inhibitors can help some prostate cancer patients, particularly men with faulty DNA damage repair genes, such as BRCA1/2. Their work ultimately led to the 2020 FDA approval of two PARP inhibitors: olaparib and rucaparib, for men with certain genetic mutations who have metastatic castration-resistant prostate cancer (CRPC).
The team’s early clinical trial results, Knudsen says, “were phenomenal: “PARP inhibitors were life-extending in a subset of patients.” Recently, encouraging data from the UK has suggested that combining PARP inhibitors with androgen receptor (AR) blockers showed great promise” in helping a wider group of patients. Using AR blockers, such as enzalutamide, might open up the use of PARP inhibitors to men with metastatic cancer who don’t have a known faulty gene such as BRCA. “That idea is strongly supported in the ovarian cancer literature,” she says. “Ovarian cancer patients who have a BRCA mutation respond to PARP inhibitors, but so do patients who don’t have a mutation. We’ve just understood the tip of the iceberg of what these drugs can do.”
Of that early research, she adds, “100 percent was funded by PCF. That allowed us to get our initial idea into action immediately; we didn’t have to wait for the long process of getting federal funding, and that initial work led to a whole series of other discoveries.”
Getting the Research Findings to the Patients
There is more hope for people diagnosed with cancer today than ever before. “We have seen a more than 30 percent decline in cancer deaths over the last few decades,” says Knudsen. “We are making progress. We know it’s tied to research: the trajectory for cancer mortality is fundamentally changed by investing in cancer breakthroughs. Now is the time to accelerate research – but also to make sure everyone has a fair chance to survive cancer. PCF has funded discoveries that have led to new interventions for prostate cancer. We need to ensure that men across the country have access to those breakthroughs.”
One way to do this, she believes, is through Medicaid expansion. “We are using science to push for reimbursement. The data show that Medicaid expansion is tightly tied to improving outcomes for cancer patients.” Another example: In lung cancer, the use of biomarker testing to determine therapy is “standard of care. But it’s not happening in a lot of places, because reimbursement is not equal. ACS has a great interest in reducing cancer disparities.” And so does PCF, she adds. “I very much hope to increase the partnership between ACS and PCF, because I am part of both of these organizations, and I love both from the bottom of my heart.”
