The current invention is a novel composition of matter as well as a method for treating tumor metastasis, which utilizes the composition of matter to reduce the prevalence of the perinucleolar compartment (PNC) in cancer cells.
Metastasis is the spread of cancer from an organ to another non-adjacent part of the organism. This process is particularly important in the development of solid tumors and is responsible for the majority of deaths associated with cancer. Several molecular targets have been identified and explored for inhibition of the metastatic process, but these approaches have not yet yielded success in the clinic. The perinucleolar compartment (PNC) is a multicomponent subnuclear structure that is highly prevalent in metastatic tumors.
KU inventors have identified and further optimized a potent inhibitor that reduces PNC prevalence in prostate cancer cells at submicromolar concentrations and the cell viability is not affected. The compound also impacts in vitro migration of tumor cells, making it useful for advanced cell-based studies. The probe displays promising in vitro ADME properties and in vivo mouse pharmacokinetics, making it an ideal candidate for understanding the therapeutic value of PNC disruption as a novel approach towards combating metastasis in cancer treatment. The compound can preferentially target cancer cells before they metastasize, thus increasing the efficacy of the treatment and reducing the risk of side effects.
Treat and prevent tumor metastasis and tumorigenesis, including solid cancers.
The PNC is a metastatic biomarker located near the periphery of the nucleolus. The novel compositions in this invention target and reduce the prevalence of the PNC without affecting cell viability. Through targeting the PNC, the compositions inhibit migration and anchorage-independent cell growth of cancer cells in a dose-dependent manner.
Typically individuals whose cancer has metastasized have a poor prognosis. The current invention increases the potential of recovery in individuals with cancer by targeting cancer cells before they metastasize.
Most therapeutic options available to treat metastatic cancers lack efficacy and result in adverse side-effects. The benefit of this therapy is that it reduces the risk of metastasis through targeting a specific cancer biomarker. This targeted therapeutic approach leads to a more efficacious cancer therapy with fewer side-effects than currently available cancer treatments.
The compositions in the current invention can be used as an in-vivo tool for elucidating the molecular mechanisms that link PNC and metastatic transformation.