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Curebound

Peptide Targeted Delivery of Epigenetic Therapies in Pancreatic Cancer

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Immunotherapy

Immunotherapies & Personalized Vaccines

Ronald Evans (Salk )

Gregory Botta (MCC)

Pancreatic cancer is a devastating disease with few effective treatments. Moreover, recent immunotherapy approaches that have been remarkably successful in certain cancers have failed in pancreatic cancer. This poor performance of current therapies is in large part due to the presence of a complex cellular support network or stroma that surrounds the tumor. Importantly, the presence of the stroma compromises the immune response as well as drug delivery to the tumor. Cancer associated fibroblasts (CAFs) are major contributors to this stromal response, and as such, approaches that reduce the activities of CAFs may improve the effectiveness of existing therapies. Towards this end, we have promising findings that the epigenetic drug OTX can reduce the tumor supporting and immune suppressive actions of CAFs, however the adverse side effects of OTX are prohibitive. Here we will explore whether targeting technologies that focus drug delivery to the pancreas are able to reduce the adverse effects of OTX, and whether the therapeutic effects of this combination therapy are sufficient to enable immunotherapies. In addition, we will explore whether the existing targeting approach can be modified to selectively target the critical CAF population. These studies will be undertaken in mouse models that accurately mimic human disease, where the effects of therapy combinations on disease burden and ultimately survival will be measured. The potential of these studies to improve the effectiveness while simultaneously reducing the adverse effects of existing therapies, as well as to sensitize pancreatic cancer to immunotherapies, could profoundly increase patient survival.

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EXPLORATION

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ACCELERATION

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COLLABORATION

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CURES