Strategies for the drug discovery... This article published recently is highlighting the issues with current chemotherapies and various future methods in order to improve the efficacy of taxanes alone, in combination with immunotherapy and conjugation technology. They highlighted three major issues with the conventional cancer treatments, one adding substances to taxanes enhancing the solubility which resulted in serious side effects, second the multidrug resistance among others due to the efflux pump and third the presence of cancer stem cells responsible or metastasis. As per the preclinical studies thus far we know TH1902 internalize rapidly bypasses the MDR1 and the latest study also suggested the TH1902 inhibits the xenografts growth of Sort1 positive TNBC/ Ovarian cancer stem cells. So if the technology works in humans mirroring the preclinical findings it will bypass the issues with the conventional chemotherapy and the targeted drug delivery as per authors of this article will be an important component to consider developing new generation taxanes.
“Considering that efficacious tumor-targeted drug delivery systems are the key to advance the new-generation taxanes to become clinical drugs, this account covered taxane-based delivery systems, especially nanoparticle formulations. The progression of new-generation taxanes heavily relies on the exploration of ideal formulations and drug delivery systems. It is one of the major fields of taxane based drug development….
Based on its own “SORT1+ Technology”, TH1902 was designed and developed by Theratechnologies to treat patients with recurrent sortilin tumors that are refractory to normal therapy. It is a docetaxel linked to a sortilin receptor targeting peptide, and is currently under Phase I evaluation as a single agent treatment for all sortilin receptor positive advanced refractory solid tumors.
Several issues with the taxanes already in clinic have been identified. One of these is the use of excipients which is required to overcome their very poor aqueous solubility [9]. There have been some cases in which the use of these excipients have led to serious side effects. Once this happens, the patients must be removed from the treatment immediately. The second problem is multidrug resistance. There are quite a few major mechanisms for multidrug resistance (MDR): 1) Overexpression of efflux pumps, especially P-glycoprotein (Pgp) and multidrug resistance-associated proteins 1 (MRP1)….