MYC RNAi Nanoparticles for Metastatic Prostate Cancer Treatment

About MYC RNAi Nanoparticles for Metastatic Prostate Cancer Treatment

The MYC gene and its protein are commonly overexpressed in prostate cancer, both in the early stages of the disease, as well as during its progression and metastatic spread. The MYC gene is often aberrantly activated in many cancers and has been implicated in prostate cancer progression to therapy resistance. Therefore MYC is an excellent therapeutic target. However, MYC has traditionally been considered “undruggable” and no effective inhibitors have been identified against this driver of prostate cancer. Dr. Omid Farokhzad and his team will employ a unique nanoparticle strategy to target MYC and inhibit its downstream signaling activity on other genes. Dr. Farokhzad and colleagues have previously successfully developed targeted nanoparticle technologies and brought these from conception to human clinical trials.

To target MYC in prostate cancer, the team will develop innovative self-assembling nanoparticles for the treatment of metastatic prostate cancer. These self-assembling nanoparticles will be designed to carry an internal payload of siRNAs, or small interfering RNAs that silence the expression and activity of specific target genes. SiRNAs are short chains of nucleic acids that can be used to block the production in our bodies of proteins that cause cancer to grow. But if siRNAs are injected directly into a patient’s bloodstream, enzymes will quickly chew up and destroy this free-floating siRNA. The researchers’ nanoparticle delivery mechanism cleverly hides away siRNA in nanoparticles so the nucleic acid chains can make it safely to cancer cells, where they can go to work to eradicate the tumor.

To guide their siRNA-carrying nanoparticles directly to prostate cancer cells, the nanoparticles will be decorated on their surface with targeting agents that will specifically deliver them to prostate tumors, avoiding normal tissue. This will lessen side effects as only cancer cells or the tumor microenvironment will be affected.

Dr. Farokhzad and colleagues will evaluate the efficacy of these nanoparticles to eradicate early invasive carcinoma, advanced localized cancer, and metastatic disease in a first-in-field, genetically engineered mouse model of metastatic disease that expresses MYC. The successful completion of this project will generate a nanoparticle candidate ready for preclinical and clinical development.

What this means for patients: Dr. Farokhzad and his team will use this Challenge Award to develop a novel nano-therapeutic that delivers bits of nucleic acid called siRNAs directly to prostate cancer cells in order to eradicate those cancer cells. Their novel therapeutic will use advanced nanotechnology to target a cancer-associated gene, MYC, that has long-been considered “undruggable.” Additionally, because their unique nanoparticles will home directly to the prostate tumors, healthy tissue will remain largely unaffected and side effects will be limited.

Principal Investigator:

Omid Farokhzad, MD (Harvard Medical School)

Co-investigators:

Angelo De Marzo, MD, PhD (Johns Hopkins), Charles Bieberich, PhD (University of Maryland), Srinivasan Yegnasubramanian, MD, PhD (Johns Hopkins), Jinjun Shi, PhD (Harvard Medical School)