State: Pennsylvania

Funded by Hooters of America, LLC

Hormone therapy medicine helps lower the chance of breast cancer growing or coming back. African American breast cancer survivors say they lack information about hormone therapy. Women also say that side effects are a main reason for stopping hormone therapy. We are doing a study that will test a text message program for these women. Women who join the study will be randomly assigned to one of two groups. One group will get text messages and the other will not. The text messages have information to help women deal with side effects. We think the women getting texts will have fewer side effects and greater belief they can manage hormone therapy. We also think they will understand why hormone therapy is important. We think this will help women worry less about hormone therapy and continue taking it. With the V-Foundation funding, our main goal is to increase the number of women who join the study. We will use our current partnership with community members and social media to recruit more women. This is the first study to test a text message program for African American women on hormone therapy. It is also one of the first to use a community partnership and social media to recruit women.

Funded in partnership with WWE in honor of Connor’s Cure

Brain cancer is now the leading cause of cancer deaths in children. A tumor known as high-grade glioma (HGG) is the deadliest type. Children with HGG are treated with surgery, chemotherapy, and radiation. They often enroll in clinical trials to try new treatments. Unfortunately, most children die within two years of diagnosis. Part of the problem is that HGG tumors develop ways to resist the effects of treatments. Our recent work using promising new glioma treatments has identified a pattern of steps that glioma cells use to develop treatment resistance. Using state-of-the-art genetic testing, we saw how HGGs at first responded to new therapies but then became resistant. Resistant HGGs showed increased levels of a protein called QPRT, which can use energy metabolites like NAD+ to protect cancer cells from the therapy designed to kill them. This suggests that by stopping the protein function, we could overcome treatment resistance. We want to achieve two aims: First: to see if QPRT is active in other commonly used treatments for HGG, and also if recurring childhood HGGs typically show high QPRT levels. Second, using tumor tissue that we cultured in the lab, we identified a drug that inhibits the NAD+ pathway and reverses treatment resistance. We want to test this drug in an animal model of treatment-resistant HGG to see if it can prolong survival. Together these aims would reveal a way that HGGs resist treatment and potentially show how a drug could block this action to overcome treatment resistance in these tumors.

Funded by Hooters of America, LLC

Black Americans often do not take part in research. They also have more aggressive breast cancer and a higher death rate from breast cancer. Overall, clinical trials have led to better outcomes for patients with breast cancer. However, the lack of Black Americans in clinical trials may be one explanation for higher death rates because new treatments are not tested in their aggressive cancers. Our goal is to help the community learn more about the role of research in breast cancer, and the value of taking part in that research. We will work with trusted members of the Black American community through our partners and lay Community Ambassador (CA) program to plan three forums. At these forums, community members will be able to talk with our doctors, clinical research coordinators, and CAs to learn about breast cancer, clinical trials, and what it means to take part in research. The forums will focus on breast cancer research. They will include questions from a host as well as questions from the audience. This will allow for an open discussion about breast cancer research. The goal of the forums will be to raise participants’ knowledge about research, and increase their odds of taking part in research.

Funded in partnership with WWE in honor of Connor’s Cure

Medulloblastoma is the most common malignant brain tumor in children. There are four distinct forms of this tumor based on its gene profiles, and a form known as Group 3 medulloblastoma is the most aggressive and deadly, which accounts for 25%-30% of all medulloblastoma. Each medulloblastoma group has distinct abnormal gene expression that determines how it creates, grows, and spreads tumors. Changes in gene behavior, like overexpression or underexpression, are controlled by what is called epigenetics. Fortunately, we know how to manipulate epigenetics with drugs. Dr. Hu and his colleagues found two epigenetic components that play important roles in controlling gene expression in tumor. Interestingly, these two epigenetic components seem to work together: when one component is suppressed, the other increases, and vice versa. A gene called MYC is very active in many cancers including Group 3 medulloblastoma. In this project, Dr. Hu’s team will characterize these two epigenetic components to understand more precisely how they work, particular in controlling MYC expression, even further, they will test in the lab whether “drugging” these epigenetic factors can halt the growth and spread of medulloblastoma tumors. If this hypothesis is proven, it may be possible to use these drugs in combination to treat this devastating childhood cancer.

The V Foundation MRA Young Investigator Award

Co-funded with The Melanoma Research Alliance

Although significant progress has been made treating melanoma and the recent approval of several drugs for the treatment of advanced disease, several challenges remain.  For example, clinical responses are generally short-lived as tumors quickly become drug resistant and patients relapse. Moreover, tumors can develop drug resistance through a diverse number of molecular mechanisms, making the development of second-line therapies extremely daunting.  Therefore, it is critical to identify therapeutic targets that are common to the majority of resistant tumors.  We have recently found that a protein kinase called S6K is activated in melanomas resistant to BRAF and MEK inhibitors.  Moreover, we showed that inhibition of this protein using a triple drug combination blocked the growth of resistant tumors.  This provides strong rationale for establishing S6K as a novel target for melanoma therapy.  Notably, S6K is a common node for most resistance pathways.  We propose to investigate the role of S6K in melanoma and determine the therapeutic value of targeting this protein.  Towards these goals we will determine the consequences of blocking S6K in melanoma, identify the proteins that are regulated by S6K and use this knowledge to delineate combinatorial approaches that can lead to long-term tumor remission in a large number of melanomas, including those resistant to BRAF and MEK inhibitors.  We expect that the data generated by these studies can be quickly translated into new strategies aimed at maximizing the therapeutic efficacy of MAPK inhibitors in melanoma and provide actionable information that will guide the design of future clinical trials. 

Funded by 2017 BRCA Fund-A-Need

Inhibitors of the poly(ADP-ribose) polymerase enzymes (PARPi) represent a significant advance in ovarian cancer treatment, particularly in those with inherited BRCA1 and BRCA2 mutations. These drugs are taken by mouth, are effective, and generally have fewer side effects than chemotherapy. However, responses to PARPi are generally limited and cancers develop treatment resistance. Inhibition of the ATR kinase offer a promising solution to this problem. Inhibitors of ATR (ATRi) and PARP have distinct and complementary effects. Data from our group shows that the PARPi-ATRi combination causes complete tumor regression in BRCA2-associated ovarian cancer animal models, an effect that is superior to that observed with PARPi alone. Based on these data, we plan a clinical trial of the PARPi, olaparib with an ATR inhibitor in patients with ovarian cancer. With support from the V Foundation, we have set out to further improve this therapeutic strategy. First, we will study tumor tissue from patients enrolled on the clinical trial to identify markers that predict if the treatment will be effective. Furthermore, we will use tumor tissue from patients to create animal models and use these animal models to test ATR inhibitor combinations with different PARP inhibitors, in addition to olaparib. We will determine which PARPi is most active in combination with ATRi, particularly in the BRCA1/2 mutation subset. Finally, we will use novel protein-based techniques to better understand exactly how the ATR and PARP inhibitors work together, which will permit further improvements of this therapeutic strategy. Our goal is to develop the most effective and well-tolerated treatment of BRCA1/2-mutant ovarian cancers for which standard therapies have faltered.

Funded in partnership with the American Kennel Club Canine Health Foundation

Bladder cancer or urothelial carcinoma (UC) affects approximately 40,000 dogs per year in the US with specific breeds including Scottish Terriers, West Highland White Terriers, Shetland Sheepdogs, Beagles, and Parson Russell Terriers being over-represented. Affected dogs usually display lower urinary tract clinical signs including bloody urine, frequent urination, difficulty and pain on urinating, and urinary outflow tract obstruction. Standard of care consists of anti-inflammatory drugs either alone or in combination with chemotherapy or radiation therapy. While these treatments can lead to stable disease for 6-12 months, they rarely lead to a cure, and most dogs eventually succumb to their disease. In human medicine, urinary bladder tumors have been shown to exhibit a high gene mutational burden which directly correlates with a favorable response to immune therapies. Canine UC exhibits a similar mutational load suggesting that the disease in dogs may also be immune responsive. In this study, the investigators will evaluate the safety and effectiveness of a novel targeted, immune therapy that aims to promote a powerful immune response against a specific gene mutation (V600E B-Raf) recently identified in up to 87% of dogs with UC. The investigators hypothesize that vaccine-induced anti-tumor immune responses will lead to tumor regression and that such favorable responses will correlate with the baseline mutational burden of the tumor. The investigators will use standard immunological methods and advanced genetic sequencing technology to study systemic and intra-tumoral immune responses to identify biomarkers that may predict immunological and clinical response in dogs.