The RIS Board authorized $134,500 at its January 2016 Board meeting for 3 new sarcoma research projects through the U of M Masonic Cancer Center and three RIS Sarcoma Cancer Fellowships for the 2016-2017 Academic year. In addition the Board authorized 2016-2017 RIS Maudlin Sarcoma Scholarships for both the University of Minnesota and the Mayo Medical Schools. These awards are the direct result of the broad and deep support that RIS received from so many of you in 2015. Thank you.
The awarded research grants for 2016 are:
The impact of Beta Adrenergic receptors
Principal Investigator: Erin Dickerson Grant: $50,000
Sarcomas are often aggressive tumors with a very poor prognosis. This combined with the wide diversity of sarcoma subtypes provides both diagnostic and treatment challenges. We recently found a unifying feature among some sarcomas in the expression of beta adrenergic receptors, suggesting the importance of these receptor signaling pathways for sarcoma cell viability and tumor progression. While the role of beta adrenergic signaling is beginning to be recognized in other cancers, little is known about these signaling pathways in sarcomas. Our recent findings suggest that several sarcoma subtypes may be inhibited by blocking beta adrenergic pathways with antagonists (beta blockers). Our studies also suggest that many sarcomas synthesize the very ligands (e.g. epinephrine or adrenaline) used to activate these receptors. In this way, sarcomas may promote their own tumor growth, and beta blockade may also inhibit this process. Our finding is novel since catecholamine production by malignant tumors has not yet been described. These studies will critically advance our understanding of sarcoma progression and lay the foundation for improving the overall survival of sarcoma patients.
A better process for predicting GIST reoccurrence
Principal Investigator Amy Skubitz Grant: $23,000
Soft tissue sarcomas encompass a diverse group of malignant tumors, including gastrointestinal stromal tumors (GIST). In many cases, after a patient has had surgery and/or chemotherapy, the tumor will grow back again. There are many factors that have been used by doctors to determine whether or not a patient’s GIST will grow back. Some of these factors include: the initial size of the tumor, how fast the tumor cells were dividing, the site of the tumor on the patient’s body, and whether the tumor had ruptured before surgery could be performed. Doctors need a better way to predict which therapy an individual patient should receive. Our group and others have used gene expression patterns from patients’ soft tissue sarcomas to predict which sarcomas will metastasize. Several other studies have explored the use of gene expression patterns to predict the rate of recurrence for GISTs. In this study, we will utilize our gene sets to evaluate gene expression data that were generated from: (i) 60 GISTs from our collaborator in France, (ii) 146 GISTs that we will obtain from Italy, and (iii) other sarcomas that are publically available in the literature. We anticipate that we will be able to use our gene sets to successfully separate the sarcoma samples into subsets with different probabilities of developing metastases. This technique may be useful to better predict which sarcoma patients would benefit from adjuvant chemotherapy. These studies will lay the groundwork for our pursuit of individualized treatment for sarcoma patients.
Improving the survival rates of Osteosarcoma patients
Principal Investigator:Subbaya Subramanian Grant: $49,450
There is a critical need to identify and develop novel therapeutic targets and agents that will significantly improve the overall survival of osteosarcoma patients, the majority of whom are children and adolescents. Despite advancements in the standard-of-care-treatment, more than half of osteosarcoma patients relapse and die from metastatic disease within 10 years of their initial diagnosis, resulting in a disproportionally high years of potential life lost compared with other cancers. Cancer cells secrete extracellular vesicles (EVs) containing microRNAs (miRNAs) and other factors that contribute to the creation and maintenance of an immune-privileged microenvironment. Our preliminary results demonstrate that specific tumor-derived miRNAs can act in a non-cell-autonomous fashion to repress the host’s immune response, specifically to reduce T cell activation and function. Our hypothesis is that tumor-derived EVs are mediating the transfer of miR-503, miR-442, and miR-552 to T cells where they repress CD28 expression, thereby decreasing T cell activation and function, and contributing to the establishment of an immune-privileged tumor microenvironment. This proposal is expected to provide novel insights into the molecular mechanisms underlying poor outcomes osteosarcoma patients and establish a mechanism by which osteosarcoma cells repress the host immune response. Such results are expected to fundamentally advance our knowledge of how miRNAs regulate immune response and cancer progression. These results are expected to have a positive translational impact as this knowledge will aid in the identification of novel therapeutic targets and inform future treatment and detection strategies, thereby improving the overall survival of osteosarcoma patients.
For Listing of previous RIS Research Grants, click here.