Lead investigator: Janet Sawicki, PhD
Collaborator: Genisphere, LLC

A core frustration of most cancer treatments is that even when patients respond, they suffer major side-effects and often quickly develop treatment-resistant tumors. Ovarian cancer is a particularly challenging disease in this regard. Taking a new precision medicine approach, LIMR researchers have developed a safe and effective nanocarrier-based therapy that specifically targets ovarian tumor cells and blocks a central mechanism of drug resistance (siHuR-3DNA). Preclinical proof of concept suggests that targeting this mechanism via this nanocarrier agent may offer safe and effective treatment of a variety of solid tumors exhibiting drug resistance.

Technology description

The cancer cell-targeted siRNA nanoparticle that has been developed employs a pharmacologically unique nanocarrier (3DNA® technology) that exhibits an affinity for solid tumor microenvironments further tunable by targeting elements. In siHuR-3DNA, tumor targeting is provided by a transferrin conjugate, and therapeutic targeting is provided by siRNA to HuR, a powerful modifier of inherent and acquired resistance to cytotoxic cancer drugs.

In a model of metastatic ovarian cancer, where drug resistance is a common barrier to effective management, infusion of this nanotherapy leads to rapid accumulation in and eradication of tumors, safely extending survival of the host. This agent is at a pre-IND development stage.

Business opportunity

siHuR-3DNA offers a broad-based precision medicine approach to the problem of therapeutic resistance, one of the most important challenges in clinical oncology. HuR is a core modifier that represents the latest edge in addressing this challenge, with broad evidence of pathophysiological relevance in ovarian, pancreatic, lung, brain, colon and prostate tumors.

Focusing only on ovarian cancer, more than 22,000 cases are diagnosed every year, with more than14,000 dying each year from the disease. The present standard of care—surgical debulking followed by chemotherapy—yields early favorable responses. But drug-resistant disease that often arises can be mainly untreatable, leading to a dismal 27 percent five-year survival rate. As is the case in many advanced cancers, there are no effective therapies for drug-resistant recurrent tumors or for tumors that do not respond to initial therapy.

The global market for ovarian cancer treatment is expected to increase from about US $1 billion in 2016 to US $4.5 billion in 2022, according to the market research firm Grand View Research.

Intellectual property position

siHuR-3DNA: Pending patents (co-invention with Genisphere, LLC)

Relevant publications

Huang YH, Peng W, Furuuchi N, Gerhart J, Rhodes K, Mukherjee N, Jimbo M, Gonye GE, Brody JR, Getts RC and Sawicki JA. (2016). Delivery of therapeutics targeting the mRNA-binding protein HuR using 3DNA nano-carriers suppresses ovarian tumor growth. Cancer Res 76: 1549-59.