These researchers have dedicated their careers to finding new treatments and cures for people with cancer.
Prostate cancer is the second leading cause of cancer-related death among men in the U.S.* and the fourth most diagnosed cancer worldwide.* While the standard treatment — androgen deprivation therapy (ADT) — targets prostate cancer even in its advanced stages, most patients rapidly develop resistance to ADT. This means it stops working as effectively. To make matters worse, these patients often experience side effects like fatigue, anemia, bone loss, and erectile dysfunction. Such adverse events can lead to decreased quality of life and poorer survival outcomes.
It’s a reality that Conquer Cancer grant recipient Dr. Isaacsson Velho, hopes to change. As an adjunct assistant professor at the Johns Hopkins Hospital in Baltimore, Md., and a medical oncologist at the Moinhos de Vento Hospital in Porto Alegre, Brazil, Dr. Isaacsson Velho dedicates his research to bringing more tolerable and effective treatments to his patients, most of whom have limited options beyond standard care. He works to uncover biological clues that flag whether patients’ bodies are resisting against or responding well to treatment.
“This area of cancer research must be accelerated due to prostate cancer's heterogeneity, which can lead to resistance against certain treatments,” Dr. Isaacsson Velho says. “This makes it imperative to develop a range of therapies to combat various forms of the disease and overcome the resistance to ADT.”
Finding New Biomarkers in Prostate Cancer
Many new studies point to DNA-related culprits that may cause immune systems to stubbornly resist ADT. Dr. Isaacsson Velho is building on this research to evaluate new treatment approaches, including some that are already proving effective in other areas of cancer care.
“Unfortunately, after some time, virtually all patients on ADT progress to a state called castration-resistant prostate cancer (CRPC), and survival ranges two to three years,” he explains. “New effective treatments are needed to prolong survival and improve quality of life.”
Growing evidence suggests that certain tumors show increased programmed cell death protein 1 (PD-1) pathway expression, Dr. Isaacsson Velho continues. These traits have proven to help doctors predict how patients will respond to immunotherapy in other cancer types. Recognizing this, Dr. Isaacsson Velho investigates whether nivolumab, a promising type of immunotherapy, could potentially benefit a subset of patients with prostate cancer patients. “By targeting PD-1 pathways, nivolumab has shown efficacy in various cancer types,” he says, “and its use in prostate cancer with DNA repair defects warranted exploration.”
Supported by a Conquer Cancer grant, Dr. Isaacsson Velho launched a clinical study on the effectiveness of nivolumab for targeting a certain type of metastatic prostate cancer. The grant funding allowed him and his team to enroll 38 patients in the study; to implement genomic sequencing techniques; and to assess tissue samples for PD-L1 genetic expression. Leveraging this immunotherapy and finding potential signals of treatment success resulted in immense promise for future treatment strategies. Even better: Numerous patients enrolled in the study had improved health outcomes.
“The key takeaway from my Conquer Cancer-funded research was the identification of potential biomarkers of response and resistance to immunotherapy in prostate cancer patients with and without DNA repair defects, contributing to our understanding of the role of immunotherapy in this context,” Dr. Isaacsson Velho says. “Conquer Cancer funding was pivotal in elevating the quality of our biomarker analyses within our study. This breakthrough finding has significant implications for treatment decision-making and the development of personalized approaches for patients with prostate cancer.”
Identifying these signals can help oncologists to better select which patients will respond favorably to immunotherapy, ultimately improving prostate cancer outcomes and reducing exposure to ineffective treatments in certain patients. This is especially vital for patients with ADT-resistant disease.
“There is an unmet need for effective treatment options for mCRPC patients who have developed resistance to standard therapies,” Dr. Isaacsson Velho says. “Exploring the potential of nivolumab in this specific patient population offered an opportunity to contribute to the advancement of personalized treatment approaches.”
A Promising Combination Therapy for Prostate Cancer
Insights gained from this initial work informed the next steps in Dr. Isaacsson Velho’s research — a subsequent clinical trial for which he received a Conquer Cancer grant. The ongoing trial is testing the effectiveness of bipolar androgen therapy (BAT), which involves testosterone dosages, paired with radium-223 (RAD), an intravenous injection. The funding enables Dr. Isaacsson Velho and his team to administer BAT-RAD on a monthly basis for six cycles.
Through the grant-supported trial, which is currently accepting patients in the U.S. and Brazil, Dr. Isaacsson Velho and colleagues plan to evaluate the anti-tumor activity and patient tolerability of BAT-RAD combination therapy. His team is assessing overall survival and quality of life, as well as prostate-specific antigen (PSA), a sign of cancer recurrence. This research is particularly vital for patients with metastatic prostate cancer, who generally have minimal treatments avenues.
“One of the key takeaways from the CDA research, which continues to significantly impact patients, is the improved understanding and efficacy of BAT-RAD” Dr. Isaacsson Velho says. “Thus far, our work has shown this combination therapy is safe and can be a potent tool in managing mCRPC, offering a promising new strategy to patients who have previously had limited options. Through this research, we are discovering the BAT-RAD approach not only slows down tumor growth, but also mitigates some of the side effects commonly associated with standard ADT and novel hormonal therapies. This has significant implications for quality of life, allowing patients to manage their disease with fewer adverse effects and leading to improved overall health outcomes.”
Patient Impact and Next Steps
Dr. Isaacsson Velho recalls a patient who underwent immunotherapy during his Conquer Cancer-funded research and who, at the start of the study, was very symptomatic. After a few months, the patient’s PSA levels were undetectable. Seeing such positive outcomes in his patients motivates Dr. Isaacsson Velho to continue advancing prostate cancer care.
“Four years later, my patient is still doing great, without any symptoms, and continues with an undetectable PSA,” he says. “Seeing this patient reach such a good outcome made me feel absolutely delighted and provided hope that these results could be extended to other patients. I am positive that the genomic findings of this study, including this patient’s outcome, may provide new insights to help more patients in the future.”
Since launching his CDA project, Dr. Isaacsson Velho has helped design and lead two more clinical trials in collaboration with multiple institutions between the U.S. and Brazil. Both trials are pending results and show promise for advancing prostate cancer research.
“Because of Conquer Cancer’s support, I am now able to advance my research to the next level,” Dr. Isaacsson Velho says. “I can broaden the scope of my investigations, collaborate with experts in the field, and translate my findings into clinical applications for patients.”