PHILADELPHIA (July 7, 2023) — Researchers at Fox Chase Cancer Center and Temple Health were recently awarded a three year, $1.2 million grant to study sulforaphane, a promising cancer preventive agent derived from broccoli and other cruciferous vegetables, for the prevention of malignant mesothelioma.
“Because advanced cancers such as malignant mesothelioma develop resistance to therapy, there is an urgent need for preventive measures,” said Joseph R. Testa, PhD, FACMG, a professor in the Cancer Prevention and Control research program and chief of Genomic Medicine at Fox Chase, the project’s principal investigator.
“Cancer preventive interventions employing relatively nontoxic chemopreventive ‘epigenetic modifiers’ have been proposed as a logical approach,” added Testa, who also holds the Carol and Kenneth Weg Chair in Human Genetics at Fox Chase.
Epigenetics is the study of how modifications to DNA and the environment surrounding DNA impact the way genes are expressed and the stability of DNA without changing its sequence. In cancer research, epigenetics is used to understand how cancer cells react to their environment and discover ways to control those reactions.
The grant is funded through the National Cancer Institute’s PREVENT Cancer Preclinical Drug Development Program. Yuwaraj Kadariya, MD, PhD, an assistant research professor in Testa’s lab, will serve as co-investigator on the sulforaphane project.
Margie Clapper, PhD, co-leader of the Cancer Prevention and Control research program, serves as principal investigator of Fox Chase’s role as a prime contractor of the PREVENT program. Fox Chase is one of seven prime contractors in the United States participating in assessing the efficacy of preventive agents and the establishment of intermediate endpoint biomarkers.
Malignant mesothelioma is an incurable cancer of the mesothelial lining that surrounds the internal organs. Approximately 80% of cases occur in the chest; of these, asbestos exposure is the most common cause. However, there is often a long delay, frequently decades, between the time of exposure and the development of cancer.
There are no preventive interventions available currently for people who are at risk of developing malignant mesothelioma. Any agent used to prevent mesothelioma would potentially need to be administered for decades. Therefore, the ideal agent not only needs to effectively prevent the disease but must also possess an extraordinary safety profile, be affordable, and be formulated so that it can be administered orally.
Sulforaphane is characterized by the presence of an isothiocyanate moiety, a substance that is highly reactive and thought to be responsible for some of its cancer-preventive properties, Testa said.
Isothiocyanates such as sulforaphane modify epigenetic machinery and play a role in altering or reversing histone and DNA modifications, miRNA regulation, and signaling pathways that are involved in DNA damage and repair, inflammation, immune suppression, and other processes of cancer initiation, promotion, and progression.
The award will fund studies assessing the ability of sulforaphane and Avmacol, a commercially available broccoli seed and sprout extract, to prevent the formation of asbestos-associated malignant mesothelioma.
The first goal is to see if these agents prevent or significantly reduce the incidence and progression of malignant mesothelioma and prolong survival. The second is to identify biomarkers in banked tissue specimens to further assess the effectiveness of the substances. Finally, the researchers will determine if it is safe to administer sulforaphane and Avmacol for a long time.
“This is the beginning of translational research in malignant mesothelioma,” said Kadariya, who added that mesothelioma is the second most common cancer behind lung cancer in people with asbestos exposure. “This compound could be a game changer for asbestos-exposed people.”
Testa and Kadariya will be working in collaboration with Joseph Friedberg, MD, FACS, Thoracic Surgeon-in-Chief at Temple Health and co-director of the Temple Health Mesothelioma and Pleural Disease Program with Melissa Culligan, RN, MS, PhD. Friedberg conducted research on sulforaphane prior to coming to Temple.
The researchers hope that success in these preclinical studies in an animal model will lead to clinical trials in humans. These would include asbestos workers, individuals with a genetic predisposition to mesothelioma due to a heritable mutation in the BAP1 gene, and family members and others who have developed mesothelioma years after washing the asbestos-laden work clothes of occupationally exposed patients.