Jacob J. Orme, M.D., Ph.D.

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SUMMARY

Clinician and physician investigator, Jacob J. Orme, M.D., Ph.D., specializes in the care of patients with genitourinary cancers including prostate, bladder and kidney cancers. He focuses on identifying and overcoming treatment-resistance mechanisms in these cancers with a particular interest in immunotherapy resistance. Dr. Orme has discovered multiple resistance mechanisms and is leading several clinical trials to overcome them in patients with refractory cancers. His work is supported by the National Cancer Institute and Prostate Cancer Foundation.

Focus areas

• Immunotherapy resistance mechanisms. Immune checkpoint inhibitor therapy helps activate the human immune system against cancers. Unfortunately, most cancers are resistant to immunotherapy and all cancers eventually develop resistance to immunotherapy. Dr. Orme's team discovered that soluble PD-L1 (sPD-L1) is released by cancerous cells through proteases ADAM10 and ADAM17. They have gone on to develop novel treatments that help prevent the activity of sPD-L1 and other immunosuppressants to rescue cancer immunotherapy in multiple cancers.
• Biological treatment-resistance mechanisms. Cancer is a constantly evolving entity. Even a single cancer cell has the potential to develop resistance that leads to progression with associated morbidity and mortality. Dr. Orme and his colleagues are working to discover treatments to overcome specific resistance mechanisms in clinical use. In addition, they develop biomarkers to help identify patients whose cancers are evolving toward resistance. These discoveries have led to clinical trials testing combination therapies and novel therapeutics.
• Helping patients live longer and better lives. No investigative work matters unless researchers can help patients to live longer and better lives. Dr. Orme's focus is to discover new treatment methods. He strives to make treatments both more effective and more easily tolerated than the harsh chemotherapeutic agents that have been used historically. His research group understands that every cancer is different. They believe that novel targeted treatments have the potential to extend and improve lives over decades rather than days.

Significance to patient care

Dr. Orme's team develops new therapeutic approaches for people whose cancers have developed therapy resistance. These treatments will help extend and improve the lives of patients with cancer.

Professional highlights

• Donald C. Balfour Award for Meritorious Research, Mayo Clinic Alumni Association, 2023.
• Innovation Accelerator Award, Office of Translation to Practice, Mayo Clinic, 2022-2023.
• Excellence Through Teamwork Award, Mayo Clinic, 2022.
• Young Investigator Award, Prostate Cancer Foundation, 2022.
• Outstanding Fellow Award, Minnesota Society of Clinical Oncology, 2021.