The Future of Cancer Discovery

Ruben A. Mesa, M.D., FACP, serves as the executive director of the Mays Cancer Center, home to UT Health San Antonio MD Anderson.

Leading the Nation’s Cancer Research for Latinos

Cancer does not discriminate, but socioeconomic status does. According to the American Cancer Society, socioeconomic status is the most critical factor affecting cancer prognosis in the U.S., impacting underlying cancer risk factors, access to insurance, preventive care, early detection, and treatment. Thus, the most effective new cancer discovery would be how to address this problem. Finding ways to overcome the deficits caused by region, ethnicity, income, and education would save more lives than any new cancer drug currently being tested.

The future of discovery at the Mays Cancer Center, home to UT Health San Antonio MD Anderson, is to make sure nobody is left behind when it comes to quality cancer care. “One of our greatest strengths is our ability to inform the rest of the world regarding the issues of cancer in Latino patients,” says Executive Director Ruben A. Mesa, M.D., FACP.

“We are looking at those issues from every angle, and we are uniquely positioned since we are a Hispanic-majority community with our region being almost 70 percent Hispanic. We look at how issues of culture and genetics impact cancer risk in Latinos in terms of cancer prevention, screenings, and what types of cancer they get. We look at how they respond to treatment, toxicity issues and even survival rates,” Dr. Mesa says.

The Mays Cancer Center is uniquely poised to address this problem, as one of only four National Cancer Institute-Designated Cancer Centers in Texas and the only one in South Texas.

Four Key Strategies to Increase Cancer Survival in Latinos:

Communicating the science of cancer in Latinos: There was no national mechanism to share discoveries in Latino cancer. The Mays Cancer Center organizes the international meeting, Advancing the Science of Cancer in Latinos conference, led by Dr. Mesa and Amelie G. Ramirez, Dr.P.H., chair of the Department of Population Health Sciences in the Joe R. and Teresa Lozano Long School of Medicine. This meeting also led to a biannual textbook on the science of cancer in Latinos, edited by Dr. Ramirez, who serves as associate director for community outreach and engagement for the Mays Cancer Center.

The Mays Cancer Center, home to UT Health San Antonio MD Anderson, is the only NCI-Designated Cancer Center in South Texas.

South Texas-focused cancer research: The field of oncology has been slow to recognize that cancer can be biologically different in Latinos. They have higher incidences of liver, stomach, prostate and breast cancer than other ethnicities, and they often do worse with the same stage of disease than Caucasians. The Mays Cancer Center is uncovering molecular weakness within these cancers in Latinos that can be leveraged therapeutically to improve outcomes.

Patient-centered complex cancer care: The center is integrating cancer care with the most modern methodologies while still being mindful of issues of geography and culture in the underserved communities of South Texas.

Next generation of cancer therapy: Latinos have high incidences of cancers deriving from inherited or acquired defects in DNA repair, such as BRCA1-mutant breast and ovarian cancers. The defects in DNA repair require the cancer cell to become addicted to back-up pathways of DNA repair to survive that normal cells do not need. The Mays Cancer Center has recruited a world-renowned group of scientists who are identifying new drugs that inhibit these back-up pathways.

“Liver cancer is one of the most disproportionately overrepresented cancers in our region,” says Dr. Mesa. Hepatocellular carcinoma (HCC), the most common liver cancer in adults, has a two- to four-times higher incidence in South Texas Latinos compared to the general U.S. population. “We’re trying to understand all aspects of that. Is it related to NASH (fatty liver)? Is fatty liver the main driver of that difference, and how are genetics factoring in?”

With the help of the University Transplant Center (a partnership with University Health System) to provide cancerous liver tumor samples, LuZhe Sun, Ph.D., is part of a research team identifying the driver mutations in liver cancers in Hispanic patient samples so they can be targeted for therapeutics. Early studies reveal Hispanic patients do have unique gene mutations that drive dysregulated metabolic pathways that are not the same profile as Caucasian patients.

Dr. Ruben Mesa is an international expert on myeloproliferative neoplasms (MPNs). His work has led to FDA approval for several cancer drugs.

Other Novel Cancer Discoveries

Dr. Mesa says the DNA repair discoveries in BRCA1-mutant cancers of Patrick Sung, D.Phil., and Robert Hromas, M.D., FACP, will be critical for the next generation of cancer therapeutics, but other novel discoveries are also making an impact:

Encapsulated rhenium for brain cancer: Andrew Brenner, M.D., a specialist in brain malignancies, developed the first nano-liposome encapsulated radioactive rhenium therapy to treat glioblastoma multiforme brain tumors, to reduce their recurrence. The radioactive molecule is administered by catheter directly into the brain tumor. Dr. Mesa says this discovery is an example of their team approach to transformational science as Dr. Brenner’s concept also involved the work of neurosurgeons to develop the delivery catheter as well as with radiologists and radiation biologists to develop the encapsulated rhenium molecule. It is currently in a Phase 2 multi-site trial led by the Mays Cancer Center.

BCG-resistant bladder cancer: Tyler J. Curiel, M.D., M.P.H., Daisy M. Skinner President’s Chair in Cancer Immunology Research, and Robert Svatek, M.D., discovered that in cases of non-muscle invasive bladder cancer (NMIBC) if you first prime with percutaneous BCG (bacillus Calmette-Guérin) vaccine before intravesical treatment, the BCG-resistance mechanism is inhibited and response is improved expanding the impact of the immunotherapy.

Phosphodiesterase inhibitors for lymphoma: Ricardo Aguiar, M.D., Ph.D., vice chief for research in the Division of Hematology and Medical Oncology, and co-investigator Enrique Diaz, M.D., are studying a promising new treatment for large B-cell lymphoma (DLBCL). Standard treatment for DLBCL involves a combination of the drugs rituximab, cycolphosphamide, doxorubicin hydrochloride, oncovin and prednisolone, termed R-CHOP. They are adding to that formulary the drug roflumilast which is an inhibitor of the phosphodiesterase 4 enzyme (PDE4). They have found that roflumilast suppresses the activity of the B-cell receptor. The B-cell receptor is hijacked by lymphoma cells to promote uncontrolled cell proliferation. Roflumilast may at the same time inhibit blood vessel growth in the tumor microenvironment and improve overall survival rates by 10 percent to 15 percent.

DNA repair inhibitors in Ewing’s sarcoma: Alexander J.R. Bishop, D.Phil., and his team at the Greehey Children’s Cancer Research Institute discovered that Ewing’s sarcoma (a childhood bone and soft tissue cancer) lacks a normal damage response mechanism because of an RNA metabolism issue that traps the BRCA1 protein usually associated with breast cancer. This leads to a DNA repair defect similar to the BRCA1-mutant cancers that can be specifically targeted in the treatment of Ewing’s sarcoma.

Nexrutine® in prostate cancer: Pratap Kumar, Ph.D., and his team are the first to show that a natural supplement (Nexrutine®) made from the bark of the cork tree can prevent progression of prostate cancer. The supplement slowed progression by 62 percent. Dr. Kumar says that a combination of this with exercise may be of even more benefit.

Momelotinib for autoimmune and myeloproliferative disorders: Both autoimmune diseases and myeloproliferative disease subvert the JAK-Stat signaling pathway to cause aberrant cell proliferation. Dr. Mesa, a nationally known clinical trialist, is leading global Phase 3 trials of numerous JAK (Janus Kinases) inhibitors, such as momelotinib, to advance treatment of auto-immune and hematologic disorders such as myelofibrosis, essential thrombocytosis and polycythemia vera. Data suggests momelotinib may inhibit hepcidin which plays a role in anemia, chronic disease, and inflammation.

Much remains to be done to address cancer outcome disparities in the Hispanic community—the largest, youngest and fastest-growing minority group in the U.S. “I feel deeply tied to this community,” says Dr. Mesa. “We serve all of South Texas and have a clear mission, and I am impressed by the vision and dedication of our leadership for really growing a world-class cancer center.”

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In the 2020 issue of Future

Future is the official magazine of the Joe R. & Teresa Lozano Long School of Medicine at The University of Texas Health Science Center at San Antonio. Read and share inspiring stories highlighting our medical alumni, faculty and students who are revolutionizing education, research, patient care and critical services in the communities they serve.

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