Targeted nano-carrier therapeutics to treat drug-resistant cancers
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. More than 22,000 cases are diagnosed every year, with more than 14,000 dying each year from the disease.
The present standard of care, surgical debulking followed by chemotherapy, yields early favorable responses. But drug resistance often arises and can be mainly untreatable, leading to a dismal 27% five-year survival rate. As is the case in many advanced cancers, there are no effective therapies for drug-resistant tumors or for tumors that do not respond to initial therapy.
Taking a new precision-medicine approach, LIMR researchers 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 central mechanism via our nanocarrier agent may offer safe and effective treatment of a variety of solid tumors exhibiting drug resistance.
The global market for ovarian cancer treatment is expected to increase from about US $1B in 2016 to US $4.5B in 2022, according to the market research firm Grand View Research.
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. 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.
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.
Stage of development
This agent is at a pre-IND development stage.
siHuR-3DNA: Pending patents (co-invention with Genisphere, LLC)
Preclinical investigations to relieve resistance to diverse modalities in cancer using siHuR-3DNA, as a single or combination component to degrade drug resistance in advanced cancers.
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.
Institutional contact: George C. Prendergast, PhD, LIMR President and CEO, 484.476.8475, [email protected]
IP manager contact: Heather Rose, PhD, JD, VP of Technology Licensing and Startups, Thomas Jefferson University, 215.503.0770, [email protected]