Medicaid Cuts Linked to Later-Stage Cancer Diagnoses

Medicaid is the largest insurance program in the United States and provides health care coverage for many low-income individuals. Medicaid is administered at the state level, and therefore, the structure and extent of coverage provided in each state varies across the country and is subject to economic policy changes.

Lindsay Sabik, PhD, Associate Professor of Health Policy and Management and member of the Hillman Biobehavioral Oncology Program, studies the impact of government policies on health care. In particular, she is interested in the role of health insurance in facilitating access to care and the impact of changes in insurance on cancer outcomes.

In a study recently published in the journal Cancer, Dr. Sabik and colleagues examined the effects of a Medicaid policy change in Tennessee in 2005. Due to financial difficulties, the Tennessee Medicaid program terminated coverage for nonelderly adults who failed to meet traditional requirements, resulting in the disenrollment of 170,000 patients. Using cancer registry data, the researchers determined that women who were diagnosed with breast cancer after the Medicaid cuts had later-stage disease at diagnosis than those who were diagnosed before the cuts. Furthermore, women living in low-income zip codes were found to have the largest increase in late stage of disease at the time of diagnosis after the disenrollment, suggesting that these women were not able to access screening services that could have facilitated an earlier diagnosis.

Watch Dr. Sabik discuss these findings in the video.

Targeting Regulatory T Cells Could Improve Cancer Immunotherapy

Immunotherapy drugs that utilize the immune system to detect and kill cancer cells have been successful against several cancers, yet they are still only effective in approximately 10 to 30 percent of patients with certain tumor types. UPMC Hillman Cancer Center researchers have recently discovered that selectively targeting a group of immune cells called regulatory T cells (Tregs) within a tumor may be a way to boost the immune system’s anti-cancer response.

Dario Vignali, PhD, Leader of the Hillman Cancer Immunology Program, Frank Dixon Chair in Cancer Immunology, and Professor and Vice Chair of Immunology at the University of Pittsburgh School of Medicine, and his colleagues discovered a few years ago that a surface protein called neuropilin-1 (Nrp1), which is expressed on almost all Tregs that infiltrated mouse tumors, was required to maintain the function, integrity and survival of Tregs within the harsh tumor microenvironment. Thus, Nrp1 on Tregs helps suppress the body’s natural anti-tumor immune response thereby helping the tumor survive. Importantly, blocking or deleting Nrp1 in Tregs in mice only impacted their function in tumors and not in the rest of the body, resulting in tumor eradication without inducing autoimmune or inflammatory disease.

More recent studies led by graduate student Abby Overacre-Delgoffe in Dr. Vignali’s lab, and published in Cell, demonstrated that tumor growth in a genetically modified mouse model in which the Nrp1 gene was deleted in only half the Treg cell population, but not the other half, was dramatically reduced when compared to a normal mouse in which Nrp1 was present in all Tregs. Genomic and cellular analyses revealed that a secreted immune molecule called interferon-gamma (IFNy) prevented the suppressive function of Tregs in the mice, particularly and selectively in the tumor microenvironment.

Using another genetically modified mouse model, they found that the role of IFNy in diminishing Treg function was crucial to the success of immunotherapies targeting the PD1 protein that have been proven to be very effective in patients.

Watch Abby and Dr. Vignali discuss this research further in the video, and read more here.

Novel Gene Editing Approach to Cancer Treatment Shows Promise in Mice

A novel gene therapy using CRISPR genome editing technology effectively targets cancer-causing “fusion genes” and improves survival in mouse models of aggressive liver and prostate cancers, UPCI researchers reported in a study published this month in Nature Biotechnology.

Fusion genes, which are often associated with cancer, form when two previously separate genes become joined together and produce an abnormal protein.The UPCI research team, led by Jian-Hua Luo, MD, PhD, Professor of Pathology and Director of the University of Pittsburgh High Throughput Genome Center, used viruses to deliver gene editing tools that cut out the mutated DNA of the fusion gene and replaced it with a gene that leads to death of the cancer cells.

Watch Dr. Luo discuss this research further in the video, and read more here.

New Study Demonstrates Synergistic Anti-Cancer Effects of Oncolytic Virus Combined with Immune Checkpoint Inhibitor

Oncolytic viruses can selectively kill cancer cells and cancer-promoting cells, either directly by binding and infecting them, or indirectly by eliciting a targeted immune response against them. UPCI investigators have been examining the anti-cancer efficacy of an immune-stimulating vaccinia virus, vvDD, and found it to be safe in humans in a phase I clinical trial. However, the overall anti-cancer effects of this treatment were limited, especially in certain tumor types that are not commonly infiltrated by immune cells, such as colorectal cancer.

In recent pre-clinical studies, a research team led by David Bartlett, MD, Bernard Fisher Professor of Surgery, Professor of Clinical and Translational Science, Vice Chairman of Surgical Oncology and Gastrointestinal Services, and Director of the David C. Koch Regional Perfusion Cancer Therapy Center, demonstrated that vvDD treatment caused tumor and immune cells to increase production of the protein PD-L1, which is involved in immune suppression. When the investigators then combined vvDD therapy with a targeted checkpoint inhibitor that blocks PD-L1, they observed a synergistic effect in which over 40% of aggressive colon and ovarian cancers were cured in mice.

Watch Dr. Bartlett discuss this research in the video, and read the journal article in Nature Communications.

Breast Cancer Patient-Led Advocate Group Awards UPCI Researcher with Leadership Grant

The Metastatic Breast Cancer Network is a volunteer, patient-led advocacy organization that seeks to address the unique needs and concerns of women and men who are living with metastatic or stage IV breast cancer. One of the ways in which the MBCN makes an impact in this area is by supporting metastatic breast cancer research through contributions made in memory of patients whose lives were cut short by the disease.

Steffi Oesterreich, PhD, Professor of Pharmacology & Chemical Biology, was selected as a 2017 recipient of a $100,000 Metastatic Breast Cancer Research Leadership Award from the MBCN for her important work towards understanding the molecular mechanisms of invasive lobular breast cancer (ILC). This subset accounts for 10 to 15% of all breast cancers, and was recently shown to have unique genomic alterations as well as etiological, biological, and clinical differences from the more common breast cancer subtype, invasive ductal carcinoma. With funds from the award, Dr. Oesterreich plans to examine metastatic ILC tissues to identify unique driver mutations that might be targeted by novel therapies.

A hub for ILC research, the University of Pittsburgh Cancer Institute held the first International Invasive Lobular Breast Cancer Symposium in September 2016, bringing together researchers, patients, and advocates from all over the world for discourse on ILC research and challenges.

Watch Dr. Oesterreich discuss ILC research and advocacy at UPCI in the video, and learn more here.

UPCI First to Explore Genetic Cancer Test to Offer Safe Thyroid-Preserving Surgery

Pittsburgh scientists and doctors are embarking on the first-ever clinical trial to determine if a genetic test they pioneered could successfully spare patients with nonaggressive thyroid cancer from complete removal of their thyroid, a butterfly-shaped gland in the neck that is important to hormone regulation and development. Such thyroid-preserving surgery minimizes surgical complications, and many patients also may avoid taking medication every day to keep thyroid hormone levels in check.

The two-year trial, which is entirely philanthropically funded by individual donors affected by thyroid cancer, will investigate whether the locally-developed molecular genetic test ThyroSeq can correctly differentiate between thyroid cancers most likely to spread and need complete removal of the thyroid gland, and those likely to be far less invasive, warranting a thyroid-preserving surgical approach.

Watch Linwah Yip, MD, Assistant Professor of Surgery and principal investigator of the trial, discuss this study, and learn more here.

Preventive Cancer Vaccines Harness the Immune System to Defend Against Cancer Development

While it is commonly known that vaccines can be used to prevent infectious diseases, researchers have also been exploring the use of vaccines for cancer prevention. Olivera Finn, PhD, Distinguished Professor of Immunology and Surgery, has dedicated her career to the study of the human immune system and how it can be harnessed to combat cancer.

While some cancer vaccines focus on attacking cancer cells that have already formed, preventive cancer vaccines aim to destroy pre-malignant cells before they turn into cancer. Dr. Finn and colleagues completed the first ever clinical trial testing a vaccine based on a human tumor antigen, MUC1, in people at high risk for developing colon cancer. The positive results of that study led to a second, larger trial that is currently ongoing.

This past year, Dr. Finn was the recipient of an Outstanding Investigator Award from the National Cancer Institute, providing $6.2 million over seven years to support her research in the immunoprevention and immunosurveillance of human non-viral cancers. She also recently received the American Association of Immunologists Lifetime Achievement Award.

Watch Dr. Finn discuss preventive cancer vaccines in the video.

UPCI Study Underlines the Importance of Routine Skin Cancer Screening

Skin cancer is the most common type of cancer worldwide. The most deadly form of skin cancer, melanoma, kills about 10,000 Americans per year. Routine screening enables earlier detection of skin lesions, when they are thinner and localized and can be removed by a simple surgical procedure. A large screening study performed at UPCI provided evidence that the benefits of routine screening by primary care physicians outweigh the risks, which may inform future screening guidelines and recommendations.

Watch Laura Ferris, MD, PhD, Associate Professor of Dermatology, discuss this work, and read more here.

Key Mechanisms of Cancer, Aging and Inflammation Uncovered

A team of researchers led by Patricia Opresko, PhD, Associate Professor of Environmental and Occupational Health at Pitt, and member of the UPCI Molecular and Cellular Cancer Biology Program and Carnegie Mellon University Center for Nucleic Acids Science and Technology, has uncovered new details about the biology of telomeres. These DNA “caps” protect the tips of chromosomes and play key roles in a number of health conditions, including cancer, inflammation and aging. Telomeres are shortened every time a cell divides and therefore become smaller as a person ages. When they become too short, telomeres send a signal to the cell to stop dividing permanently, which impairs the ability of tissues to regenerate and contributes to many aging-related diseases. In contrast, in most cancer cells, levels of the enzyme telomerase, which lengthens telomeres, are elevated, allowing them to divide indefinitely.

A number of studies have shown that oxidative stress—a condition where damaging molecules known as free radicals build up inside cell—accelerates telomere shortening. Free radicals can damage not only the DNA that make up telomeres, but also the DNA building blocks used to extend them. New findings by the research team suggest that the mechanism by which oxidative stress accelerates telomere shortening is by damaging the DNA precursor molecules, not the telomere itself. Mediation of these biological activities may provide new approaches for treating cancer.

Watch Dr. Opresko further discuss their findings in the video, and read the press release here to learn more.

Dr. Stanley Marks Honored with Endowed Chair in His Name to Recruit Cancer Leaders

Stanley Marks, MD, a leading UPMC oncologist and advocate for cancer patients throughout the western Pennsylvania region, was honored this month by UPMC and his medical partners at Oncology Hematology Association (OHA) through the establishment of the Stanley M. Marks – OHA Endowed Chair in Hematology/Oncology Leadership. The permanent endowment will support the recruitment and retention of outstanding leaders in the University of Pittsburgh Division of Hematology/Oncology. It also will help to train professionals devoted to research and improved treatments for patients.

Please watch the video, and click here to learn more.

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