At its most basic level, cancer is the result of runaway cells and an immune system under attack. While MD Anderson’s clinicians and scientists are passionate about treating and curing cancer with a laser-like focus, it’s easy for them to appreciate its connectivity with other illnesses.
MD Anderson physicians recognize that their patients are often not just cancer patients, but may bring with them a host of other health issues such as heart conditions, diabetes, Alzheimer’s disease, HIV/AIDS, alopecia areata (See related article "A career built on a fascination with T cells") and multiple sclerosis. They also understand the cellular functions commonly shared by cancer and other diseases.
Epilepsy and heart attacks
Take epilepsy for example. While studying potassium channels — the body’s electrical breaker boxes that regulate cells, cancerous or otherwise — MD Anderson’s Edward Yeh, M.D., chair of Cardiology, revealed important new findings about a gene called Sentrin/SUMO-specific protease 2 (SENP2), which is crucial to brain and heart development. It appears that SENP2 deficiency can result in spontaneous seizures and sudden, unexplained death. His study results, published in Neuron, may very well explain the most common cause of early mortality in epilepsy patients.
“Understanding the genetic basis for sudden, unexplained death is crucial, given that the rate of sudden death in epilepsy patients is 20-fold that of the general population, accounting for the most common epilepsyrelated cause of death,” says Yeh.
Yeh’s group also revealed new findings about a form of stem cell therapy used for cardiac repair. Just as stem cell therapy has become a viable option for many cancer patients, the use of mesenchymal stem cell therapy has been studied for people who’ve had heart attacks or who live with congestive heart disease. The team saw improvement in cardiac function following stem cell transplantation. Clinical trials are underway in collaboration with the Texas Heart Institute to determine whether mesenchymal stem cells can improve heart function in cancer patients who have chemotherapy-induced heart failure.
Yeh also led an atherosclerosis study with results reported in the Journal of Clinical Investigation. Like cancer, atherosclerosis is associated with cell death and inflammation. His team’s study, which focused on inhibiting a protein called SENP2, could open up new possibilities for drug targets for this common disease in which plaque builds up inside the arteries, increasing the risk of heart attack and stroke.
Targeting diseases of the elderly and chemotherapy-related nerve pain
Scientists have long known there are molecular themes common to neurodegeneration, cancer and other age-associated diseases. The Neurodegenerative Consortium, a collaboration between MD Anderson’s Institute for Applied Cancer Science, Baylor College of Medicine and the Massachusetts Institute of Technology, was launched in 2011 with a $25 million matching gift from the Belfer Family Foundation. The foundation followed up with another $5 million gift in 2015.
The consortium was initiated to share promising discoveries across the three institutions with the goal of developing the next generation of targeted drugs and diagnostics for illnesses associated with advanced age such as Alzheimer’s disease, ALS, and Huntington’s and Parkinson’s diseases. It’s hoped discoveries will also address chemotherapy-induced neuropathy, a painful condition for many cancer patients.
“The large numbers of MD Anderson patients who suffer from this side effect provide an opportunity for collaboration between their physicians and researchers to better understand the underlying biology associated with neuropathy,” says Ronald DePinho, M.D., president of MD Anderson. “Such a discovery could lead to the development of prevention and treatment strategies.”
Finding a protein linked to multiple sclerosis and inflammatory diseases
Multiple sclerosis patients could benefit from a study that identified potential therapeutic targets for a devastating disease striking some 2.3 million people worldwide.
The study was led by Shao-Cong Sun, Ph.D., professor of Immunology at MD Anderson. Sun’s findings, published in Nature Immunology, identified a protein regulator known as Trabid as an important piece of the puzzle that leads to autoimmune inflammation of the central nervous system in multiple sclerosis patients.
Inflammation is an important part of the body’s response against infections and tissue damage, but unresolved inflammation promotes cancer development and can be a contributing factor in a variety of diseases.
A diabetes drug for cancer?
Since the mid-1990s, metformin has been prescribed for Type 2 diabetes. The popular and inexpensive drug works by impacting cell signaling pathways directly or indirectly at several locations in the body. The commonality between diabetes and cancer appears to be obesity.
Scientists at MD Anderson believe metformin may benefit women with breast cancer. A study by Experimental Therapeutics’ Enrique Fuentes-Mattei, Ph.D., compared a newly developed obese-mice model with breast cancer and biological changes in breast cancer samples from patients. The results indicated a tie between obesity and a more rapid onset of disease and higher rate of death for women with estrogen-positive (ER+) breast cancer.
“Obesity increases the risk of cancer death among postmenopausal women with ER+ breast cancer, but the direct evidence for how this occurs is lacking,” says Fuentes-Mattei, whose study results were published in the Journal of the National Cancer Institute. “Our study reported direct evidence about the breast cancerpromoting impact of obesity, which is like jet fuel for cancer.”
Fuentes-Mattei’s team found that fat cell proteins known as adipokines change the gene expression profile in breast cancer cells, promoting tumor growth and proliferation. The researchers also revealed that metformin, when combined with the targeted-therapy drug everolimus, suppressed fat cell-induced tumor growth in the obese mice and secretion of adipokines by fat cells.
“We believe that our mouse model will be a useful tool for future research on the development of therapeutic strategies that would block or reverse the effect of obesity on cancer,” says Sai-Ching Jim Yeung, M.D., Ph.D., professor of Emergency Medicine and senior co-leader of the study with Mong-Hong Lee, Ph.D., professor of Molecular and Cellular Oncology.
An MD Anderson clinical trial based on the study is being led by Vicente Valero, M.D., professor of Breast Medical Oncology.
Aung Naing, M.D., associate professor of Investigational Cancer Therapeutics, has also studied metformin and conducted a combination clinical trial that paired metformin with temsirolimus, a chemotherapy drug.
Additional MD Anderson studies are focusing on metformin and other diseases such as lung and endometrial cancer.
Seeking a sickle cell treatment alternative Priti Tewari, M.D., assistant professor of Pediatrics, is an oncologist who specializes in stem cell transplantation for malignant and nonmalignant pediatric diseases. She and her colleagues treat conditions such as anemia, clotting disorders, hemophilia, leukemia, lymphoma and sickle cell disease (SCD).
SCD is a group of inherited disorders in which red blood cells form into a crescent shape, like a sickle, and break apart easily, causing anemia. The damaged cells also clump together and stick to the walls of blood vessels, blocking blood flow. This can cause severe pain and permanent damage to the brain, heart, lungs and other organs. The disorder affects 90,000 to 100,000 people in the United States, primarily African-Americans and Hispanics.
Tewari’s interest in sickle cell disease led to a clinical research trial that is studying the safety of giving NiCord® as an alternative therapy to the standard bone marrow transplantation prescribed for many patients with blood disorders. NiCord® is an umbilical cord stem cellbased treatment.
New findings about an ancient disease
The word “leprosy” often conjures up images of Biblical suffering or sanitorium settings. And yet the illness, properly known as Hansen’s disease, continues to strike hundreds of thousands of people worldwide each year, primarily in developing countries.
An MD Anderson pathologist, Xiang-Yang Han, M.D., Ph.D., professor of Laboratory Medicine, has studied mycobacterium lepromatosis, a species of bacteria he first reported in 2008 as another cause of the disease. Up to that point, the only known cause of Hansen’s disease was mycobacterium leprae.
In studying 20 genes of mycobacterium lepromatosis in comparison with mycobacterium leprae, Han found that the two bacteria came from a common ancestor some 10 million years ago. No one knew how long the disease had existed, but Han’s work clearly showed it is, indeed, an ancient disorder, with its genetic beginnings as old as 20 million years.
This discovery offers new insights into disease pathogenesis beyond Hansen’s disease, a finding that has implications for cancer microbiologists like Han.
“Many patients who come to MD Anderson suspected of having cancer turn out to have infections instead, and we make game-changing diagnoses nearly every day.”