"Every day our results generate new hope"
People come from all over the world to the Molecular and Experimental Medicine laboratory of Brunhilde “Brunie” Felding, PhD. Some are breast cancer patients, many of them diagnosed with different cancers that are very aggressive. Others are pharmaceutical company representatives seeking the next promising drug. Still others are philanthropists interested in supporting her very promising research. As one industry executive recently put it, Felding’s steady progress toward first identifying and now developing a drug to halt metastasis, the feared spreading of cancer, is nothing short of “remarkable.”
While investigating the underlying mechanisms of cancer progression, Felding discovered a defect in mitochondria, the powerhouses of the cell, within aggressive breast cancers. That defect impairs cellular respiration and disturbs the balance between two forms of a key metabolic coenzyme: NAD+ and NADH. As a result of that imbalance, the tumor cells become very aggressive; they invade and metastasize.
Research in mouse models showed that by providing the animals with a precursor for NAD+ production, such as nicotinamide riboside, levels of NAD+ rose. Significantly, this simple treatment inhibited cancer progression and reduced metastasis, prolonging life. Even better, the precursor treatment is already known to be safe for humans. Encouraged by the striking results of those preclinical studies, the Felding group is now integrating the NAD+ precursor approach with standard of care cancer treatments. Promising results indicate that combining NAD+ precursors with endocrine therapy for estrogen receptor positive breast cancer, or with radiation therapy of metastatic lesions to the brain, boosts treatment efficacy and helps prevent disease recurrence.
Because the disease is deadly and the need for a cure so great, Felding continues her investigations into cancer’s mechanisms of metastasis. She emphasizes that “tackling such an aggressive and complex process takes extraordinary effort and can be achieved only through teamwork." Bringing together and leveraging the unique expertise prevalent at Scripps Research, Felding and her colleagues are developing new, highly specific antibody-based treatments for very aggressive cancers that currently lack targeted therapies. Leaders in antibody engineering, chemistry, protein structure analysis, bioinformatics and cancer biology are teaming up to build a personalized cancer treatment program by identifying unique targets in someone’s cancer, generating highly efficient and specific antibody drug conjugates, and following treatment responses and disease progression in patient blood samples. The goal is to outrun cancer progression and provide patients with highly efficient treatments that have minimal side effects and a lasting impact to achieve a cure.
Every day our results generate new hope,” Felding says. “Our team efforts are yielding amazing progress—despite the hard challenges that cancer puts up. Another critical motivator, without which we could not press on and stay on target, comes from close interactions with people having a cancer experience. We always make time to welcome visitors to our lab, especially when they’re breast cancer survivors. That brings home why we’re doing this research.