To highlight some of the advances being made against cancer by American Cancer Society-funded scientists, our Research department wants to answer the simple question, “Why does it matter?” about various extramural research developments around the country. 

These “Why does it matter?” articles aim to briefly summarize recently published work from current or past ACS funded scientists across the United States, emphasizing the progress research is making in the prevention, detection, and treatment of cancer, and quality of life for cancer survivors. 

Here are some brief summaries of relevant research from our six Extramural Programs, as well as from the ACS Professors program, and why it matters:

Extramural Research Program: Clinical Cancer Research, Nutrition, and Immunology

• Why Doesn’t Immunotherapy Always Work? It’s a powerful idea: Use your own immune system to fight cancer. But why don’t immunotherapies work the same for all cancers? Former ACS grantee Dr. Padmanee Sharma and colleagues at MD Anderson Cancer Center in Houston are working to answer this question for glioblastoma multiforme, an aggressive cancer of the brain and spinal cord. Sharma’s team studied immune cells that are found in and around human tumors that either did or did not respond to immunotherapy. She discovered that a unique population of immune cells actually stopped immunotherapy from working in glioblastoma. However, in a mouse model, when these unique cells were not present, immunotherapy was more effective, and the mice survived longer. This study has two major impacts. First, Sharma may have found a potential therapeutic target to help immunotherapy work better for glioblastoma. Second, it shows that starting with what we know – in this case, the kinds of immune cells that surround tumors – can help generate hypotheses that can be tested in the lab and rapidly translated to clinical trials.
• What comes next?  To test whether therapeutic removal of the inhibitory cells (CD73+) will work in human cancers as it did against mouse brain tumors to convert unresponsive cancers into tumors that are effectively eliminated by immunotherapy.
• Read more about this study.

Extramural Research Program: Health Professional Training

• Improvements in the Management of Long-Term Effects of Cancer Treatment: If you are a survivor of cancer that was diagnosed when you were a child, teenager, or young adult, your chances of living a cancer-free life are very good thanks to advances in treatment. Unfortunately, you may experience significant and permanent side effects. Hearing loss is a common side effect of radiation and chemotherapy treatments, but we don’t know much about how these patients experience it and what impact it has in their lives. Emily Tonorezos, MD, MPH and other researchers affiliated with the Adult Long-Term Follow-up Program at Memorial Sloan Kettering Cancer Center in New York City interviewed adult survivors of childhood and young adult cancer to gain insight into their “lived experience” (or perception of their health-related experiences) of hearing loss. They learned that survivors don’t know that they may have hearing loss, may feel isolated or excluded in social settings as a result, and may downplay hearing loss compared to the threat from their cancer. Because hearing loss is often described as an “invisible condition,” clinicians should ask survivors about it so that they can get help. 
• What comes next? Educating healthcare professionals about these findings may help improve quality of life for survivors of cancer diagnosed when they were young.
• Read more about this study.

Extramural Research Program: Translational Cancer Research

• A Model to Accelerate New Treatments for Wilms Tumor in Children: Despite successes in treating Wilms tumor (WT), the most common kidney cancer in children, some of these tumors are associated with poor outcomes. We know which WTs tend to be high-risk – those that come back after treatment, develop in both kidneys (bilateral), or are composed of cells that don’t resemble kidney cells and structures (diffuse anaplasia). But we don’t have treatments that work well, mainly because we don’t have good ways to test them on WTs. Former ACS grantees Drs. Rani George (Dana Farber Cancer Institute), Jeffrey Dome (Children’s National Medical Center in Washington), Davidoff and Houghton (St. Jude Children’s Research Hospital in Memphis), and others may have developed a model that can help. It involves removing pieces of WT from 45 patients and grafting them into mice, where over time the tumors continue to “act” like they do in the human patient. Comparison of the patient-derived tissues (before and after engraftment), particularly in response to therapies, instills great confidence that the scientific community now has a valuable resource to accelerate the clinical impact of research on WT subtypes with poor outcomes.  
• What comes next?  In the very near future, we should see whether this model can more accurately predict which treatments will work best for hard-to-treat WT.
• Read more about this study.

Extramural Research Program: Cancer Control and Prevention Research

• Better Communication About Cancer Care: Palliative care is recommended as a standard part of care given to people with cancer and focuses on reducing distressing symptoms and improving quality of life for survivors, family members, and caregivers. Being diagnosed with cancer is life altering and communication plays a critical role. ACS grantee Dr Robert Gramling and his team at the University of Vermont are analyzing recorded palliative care conversations to see how survivors understand their experiences, what suffering means for them, and how decisions might affect them. This new research uses natural language processing from transcripts of palliative care consultation visits. Researchers hope the results will help improve communications between patients and their health care professionals about care they’re getting, and how to more clearly convey information about the patient’s cancer prognosis and treatment. The US Senate is currently reviewing the Palliative Care and Hospice Education and Training Act (PCHETA), and if it is passed, the findings from this study could play a role in the implementation of public policy. PCHETA aims to establish and expand palliative care workforce training for interdisciplinary health care professionals by increasing the number of permanent faculty in palliative care at accredited medical schools, nursing schools, social work schools, and other programs. The bill will also significantly enhance research in palliative care and launch a national education and awareness campaign. 
• What comes next?  The next step is to ensure that what has been learned about patient communication will be translated into the health care system to ensure that all cancer patients receive timely and appropriate palliative care. 
• Read more about this study.

Extramural Research Program: Cancer Cell Biology and Metastasis

• Guiding the Combination of Targeted and Immunotherapy in Melanoma: A major function of the immune system is to attack foreign cells while leaving the normal cells alone. To control this, it uses “checkpoints.” Immune checkpoints are molecules on certain immune cells that need to be turned on (or off) to control an attack on foreign cells like cancer cells. However, cancer cells sometimes find ways to overcome these checkpoints to avoid being attacked by the immune system. This is where drugs that target these checkpoints hold a lot of promise as cancer treatments. They are called checkpoint inhibitors. Immune checkpoint inhibitors, such as nivolumab, have improved patient survival and helped people with melanoma live longer. However, new immune targets are needed because about half of melanoma patients don’t respond to current immunotherapies. Among the possibilities is a protein called VISTA. ACS grantee Dr. Andrew Aplin from Thomas Jefferson University in Philadelphia has found that melanoma tumor cells have large amounts of VISTA on their cell surfaces, and that VISTA seems to interfere with the immune system’s ability to attack the tumor cells. Interestingly, he found that certain targeted therapies, like the drug vemurafenib, which is already approved to treat some kinds of melanoma, reduces the amount of VISTA on the tumor cells. That means it may make existing immune therapy work better for more patients. Also, knowing how much a drug affects VISTA may help researchers prioritize similar-acting drugs that could make immunotherapy work better.
• What comes next?  Since both immunotherapy and vemurafenib are already approved for melanoma, researchers should be able to test the combination quickly in patients.
• Read more about this study.

Extramural Research Program: ACS Professors Program

• Blocking Drug Resistance in Breast Cancer: Breast cancer patients with HER2 mutations will often develop resistance to cancer drugs, including the new drug called neratinib. ACS Professor Dr. Carlos Arteaga at UT Southwestern in Dallas is trying to find out why. His team created a lab model with neratinib resistant HER2 breast cancer cells. They found that a key step in developing resistance happens when another gene, called TORC1, is activated or “turned on.” When that happened, neratinib stopped working. There is already another drug (everolimus) that can stop TORC1 from being turned on. Arteaga’s team found that using the two drugs together prevented resistance to neratinib from developing. 
• What comes next?  The next step is to try this in breast cancer patients as well as other cancer types such as lung and ovarian where HER2 mutations appear.
• Read more about this study.

Extramural Research Program: Cancer Control and Prevention Research

• E-cigarette Use and Respiratory Disease: Smoking regular cigarettes accounts for about 30 percent of all cancer deaths in the United States, including about 80 percent of all lung cancer deaths. Lung cancer is the leading cause of cancer death in both men and women and is one of the hardest cancers to treat. Regular cigarettes also cause other lung diseases like asthma, bronchitis, and emphysema. Using e-cigarettes has been marketed as a less harmful alternative to smoking cigarettes. However, there’s still a lot that we don’t know about e-cigarettes. A recently published study by past ACS grantee Stanton Glantz, PhD from the University of California, San Francisco examined how e-cigarettes affect lungs. He found that e-cigarette users increase their risk of getting lung disease other than cancer by a third, compared to cigarette smokers who had a 2.5 higher chance of getting other lung diseases. His study also found that people who smoke traditional tobacco products and also use e-cigarettes, a common practice, are at an even higher risk for developing respiratory disease compared to those who use either product alone. 
• What comes next? Ensure that information provided to the public about e-cigarettes is accurate and evidence based.
• Read more about this study.

Extramural Research Program: Molecular Genetics and Biochemistry of Cancer

• Protein Turnover, a New Cancer Drug Target? As researchers have learned over the past few decades, the transformation of normal human cells into cancer cells can be highly complicated. A wide range of alterations to normal cells can lead to the development of cancer, so the more we know about how cells become cancerous, the better equipped we are to prevent, detect, and treat cancer. ACS grantee Patrick Potts at St Jude Children’s Research Hospital in Memphis, TN recently reported important new information about a protein called MAGE, that is normally only made in the testes, but found to be inappropriately made in more than a dozen different types of cancers. His laboratory has discovered that MAGE proteins cause cancer by allowing higher levels of other oncogenes to accumulate in cells leading to uncontrolled growth. The MAGE protein interferes with the normal process of turning an oncogene off and leads to abnormally high levels of these growth stimulating factors, which causes cells to grow out of control. This discovery opens the door for developing new drug that focused on stopping these MAGE proteins from causing the uncontrollable growth of cancer cells. 
• What comes next?  Over the next few years we expect to see a new class of cancer drug tested that target restoration of normal protein turnover.
• Read more about this study.