While certain therapies are effective in the treatment of colorectal cancer (CRC), some forms of this cancer spread to the liver and also cause further harm.   Funding for this new endeavor allows for the development of a targeted treatment that lands on the CRC cells and delivers genetic messages, turning them into cancer-fighting cells to prevent further spread. 

Glioblastoma is an aggressively malignant brain tumor. Current standard treatment involves a combination of surgery, chemotherapy, and radiation therapy, and is rarely curative. 

Our funding supports a new Transcriptome-Wide Association Study (TWAS) in glioblastoma treatment at the single-cell level. This research will expand our understanding of the molecular and cellular heterogeneity of glioblastoma to develop targeted therapies to better treat these brain tumors.

Our funding has revealed new ways that tumors evade the immunotherapy drug delivery process. Because of this, researchers are now better poised to improve patient outcomes for all types of cancer by guiding the development of therapies that enhance the STING protein's cancer fighting abilities while minimizing harm to immune cells. This groundbreaking research has the potential to revolutionize cancer treatment in both the short and long term.  

DIPG is a rare cancer impacting about 300 children per year in the United States.  Our funding has identified a mechanism to increase the uptake of therapeutic nanoparticles in DIPG cancer cells, a new and sophisticated process to deliver treatment to this complex brain tumor.  This new therapeutic strategy and biomarker could be relevant to other brain tumors and is currently being tested.  A patent of the biomarker will be filed as a result of these promising research findings.

Scientists learned how glioblastoma grows in its tumor microenvironment (TME) in the brain using a receptor called PTPRZ1.  Findings show that the GBM tumor is aggressive in hijacking cells outside of the original tumor creating a growing tumor.  In learning how GBM grows, scientists are learning why it is aggressive, how it grows so quickly, how the tumor reacts within the entire brain, how to better understand how to treat it with the PTPRZ1 receptor.   Understanding how the tumor grows and mutates is critical for surgery, treatment, and drug interaction with the tumor. 

Most cancer treatments — such as chemotherapy, radiation therapy and targeted therapy — work by direct killing of cancer cells. Some of the recent and most powerful therapies work by stimulating the patient’s own immune system to kill cancer cells. While these new immune-based therapies work better than most previous therapies and are now approved for treating 13 cancer types, they do not work for all patients. To understand why these treatments work for some patients and not others, we need better tools to investigate how the immune system interacts with cancer. We have developed a new way of growing tumors outside patients’ bodies to study how tumor cells and immune cells interact with each other. This research aims to study how different types of immune cells stop cancer growth, using tumors grown outside of the body to test new treatments designed to steer the immune response towards tumor cells more effectively. If initial tests are successful, we will aim to try these new treatments in patients with melanoma and potentially other types of cancer.

The results of these studies are expected to lead to combination strategies that can be explored clinically in patients resistant to immunotherapy. The resulting work with these scientists is advancing this therapy to the clinic and combination clinical trials with anti-CD38 therapeutics.

Currently, 50-65% of patients with advanced melanoma are resistant to current treatment strategies. Scientists have profiled explants in an effort to understand diverse individuals and tumors.  Doing this in the future with trials will potentially impact dozens of individuals as part of early-phase testing. Hundreds of patients with advanced melanoma not responding to cancer immunotherapy could be impacted by the successful development of novel treatment approaches.

The Duke Cancer Institute and the College of Veterinary Medicine at N.C. State University formed a Comparative Oncology Consortium (COC), taking advantage of their expertise and national leadership in their respective disciplines. This collaborative pre-clinical and clinical cancer research advanced our understanding of both cancer causation (a high incidence of specific cancers in specific dog breeds) and of behaviors and genetics of specific tumor types, as well as to coordinating clinical trials in humans and canines so that novel therapies can be tested in both settings, with information gained in one setting informing the other. The ability to use biomarkers and pharmacology in the canine models can be a novel addition to the characterization of these new cancer therapies and these insights could result in significant enhancements of clinical trial designs including dosing, scheduling, and combination therapies when these treatments are tested in human clinical trials. Cost savings and improved clinical trials encourage pharmaceutical companies to use the canine models as part of the assessment process, benefiting canine patients by giving them access to these novel therapies.

Immunotherapy has emerged as a powerful approach to treating cancer, but only a subset of patients respond, and the remainder suffer severe side effects without benefiting from the therapy. There is a critical need to understand the limiting factors in immunotherapy's success and develop strategies to enhance responsiveness. Most immunotherapies involve the killing of tumor cells by immune system cells called T-cells. For T-cells to attack tumors, the tumors must have a protein called MHC on their surface. 

This work focuses on immunotherapy for medulloblastoma (MB), the most common malignant brain tumor in children. A mutation was recently identified in the study of organoids that leads to the loss of MHC on MB cells, making tumors that carry this mutation invisible to T-cells and insensitive to many immunotherapy approaches. It is unknown whether this same mutation causes loss of MHC in human MB - if so, patients with this mutation might be unresponsive to immunotherapy. Importantly, research also identified proteins that can restore MHC expression in tumor cells carrying the mutation.

This study hypothesizes that these proteins could be used in conjunction with immunotherapy to turn on expression of MHC and render tumors more sensitive to T-cell attack. If successful, the work proposed here will pave the way toward more effective use of immunotherapy for patients with MB and other pediatric cancers.