A multiscale model to design therapeutic strategies that overcome drug resistance to TKIs in multiple myeloma.

A multiscale model to design therapeutic strategies that overcome drug resistance to TKIs in multiple myeloma. Math Biosci. 2019 Dec 03;:108293 Authors: Bouchnita A, Volpert V, Koury MJ, Hellander A Abstract Drug resistance (DR) is a phenomenon characterized by the tolerance of a disease to pharmaceutical treatment. In cancer patients, DR is one of the main challenges that limit the therapeutic potential of the existing treatments. Therefore, overcoming DR by restoring the sensitivity of cancer cells would be greatly beneficial. In this context, mathematical modeling can be used to provide novel therapeutic strategies that maximize the efficiency of anti-cancer agents and potentially overcome DR. In this paper, we present a new multiscale model devoted to the interaction of potential treatments with multiple myeloma (MM) development. In this model, MM cells are represented as individual objects that move, divide, and die by apoptosis. The fate of each cell depends on intracellular and extracellular regulation, as well as the administered treatment. The model is used to explore the combined effects of a tyrosine-kinase inhibitor (TKI) with a pentose phosphate pathway (PPP) inhibitor. We use numerical simulations to tailor effective and safe treatment regimens that may eradicate the MM tumors. The model suggests that an interval for the daily dose of the PPP inhibitor can maximize the responsiveness of MM cells to the treatment with TK...
Source: Mathematical Biosciences - Category: Statistics Authors: Tags: Math Biosci Source Type: research