Cancer Treatment Agents Summary

Research at Childrens Hospital Los Angeles has led to the development of proprietary chemotherapeutic treatment regimens that are effective against multi-drug resistant cancers and are p53-independent, but cause minimal toxicity.  Childrens Hospital Los Angeles holds the intellectual property around these technologies to ensure a defendable commercial opportunity.

Cell membranes contain a wax-like molecule (ceramide) that plays a unique role in regulating the cytotoxic response to chemotherapy drugs.  An imbalance of this molecule within a cell triggers cell death by apoptosis and by non-apoptotic mechanisms.  Fenretinide (4-HPR) is a synthetic retinoid that has proven cytotoxic properties at low concentrations in numerous cell lines, and acts by disrupting ceramide metabolism.  A sub-optimal oral 4-HPR formulation, available from the NCI, is currently undergoing Phase II blinded trials in neuroblastoma, ovarian and prostate cancer.  This available formulation of 4 HPR has very poor bioavailability, and, as a result, has significant limitations.  A novel proprietary intravenous formulation of 4 HPR, developed by Childrens Hospital Los Angeles investigators, that has significantly improved bioavailability and pharmacokinetic properties, has completed pre-clinical development and is currently in Phase I trials.  In addition, an improved and proprietary oral formulation is also under clinical development.

New drug combinations that generate and/or modify ceramide production are also under investigation.  Two ceramide modulating agents have been identified that are currently in pre-clinical development; Childrens Hospital Los Angeles has filed patents on these agents.  Furthermore, the cytotoxic effects of 4 HPR can be enhanced by administration of an agent that manipulates ceramide metabolism and cellular control of ceramide-generated cytotoxicity.  It is anticipated that combinations of 4-HPR and one or more ceramide modulating agents will result in even greater tumor cell kill with minimal toxicity compared to current chemotherapies utilized today.

Barry Maurer, MD, PhD and C. Patrick Reynolds, MD, PhD, Division of Hematology and Oncology, Childrens Hospital Los Angeles.  Drs. Maurer and Reynolds are lead investigators in the Cancer Program at Childrens Hospital Los Angeles, and are nationally and internationally recognized experts in cancer developmental therapeutics.