Tumor resistance in cancer is the principal driving force behind the ineffectiveness of therapeutic agents and poor patient survival. Tumor resistance and the recurrence of tumors after treatment with anticancer drugs is generally considered to result from genetic mutations, cellular switching to alternate oncogenic pathways, and the export of drugs from tumor cells by ATP-driven transporters. Although the lack of clinically durable responses and the frequent re-occurrence of invasive tumor cells in cancer patients have been primarily attributed to these, compelling research shows that major changes in the actin cytoskeleton, alterations in cell morphology and restricted brain access play critical roles in tumor resistance. Oncorx Pharmaceuticals has identified therapy-resistant tumor cells that have distinct actin cytoskeletal composition and cell morphology characteristics from therapy-sensitive tumor cells in the majority of solid tumors. Whereas existing therapies are able to regulate the progression of therapy-sensitive tumors, they cannot regulate the progression of therapy-resistant tumors having altered actin cytoskeletal composition and cell morphology characteristics. Foremost among these are glioblastoma tumors comprising mesenchymal-like spindle-shaped tumor cells. Restricted access to the brain additionally plays a prominent role in both primary glioma tumors such as glioblastoma and brainstem cancers (DIPG) as well as secondary glioma-like tumors that have metastasized to the brain.
The most intractable primary brain tumor (DIPG) occurs in children has one of the shortest life expectancies. Diffuse Intrinsic Pontine Glioma (DIPG) is a glioblastoma-like tumor in the brain stem and one of the most resistant of all cancers. DIPG primarily affects young children between 5 and 7 years old and these children survive less than one year after diagnosis. No effective treatments currently exist for DIPG. Unfortunately, restricted access to inaccessible areas of the brain such as the brainstem in DIPG further complicate surgery, radiation and drug therapy for this devastating disease.
Oncorx Pharmaceuticals has developed a novel family of brain penetrating molecules that selectively accumulate in the brainstem and disrupt F-actin cytoskeletal organization. These novel compounds are based upon similar compounds that have previously demonstrated marked effectiveness in treating gliomas in both in vitro and animal studies.