K-RAS (Transcell Oncologics)

The incorporation of bactericidal properties into textiles is a widely sought-after aspect, and silver nanoparticles (AgNPs) can be used for this. Here, we evaluate a strategy for incorporating AgNPs into a cotton fabric. For this purpose, a bactericidal textile coating based on a composite of AgNPs and kappa-carrageenan (k-CA) was proposed. The composite was obtained by heating the silver precursor (AgNO₃) directly in k-CA solution for green synthesis and in situ AgNPs stabilization. Cotton substrates were added to the heated composite solution for surface impregnation and hydrogel film formation after cooling. Direct synthesis of AgNPs on a fabric was also tested. The results showed that the application of a coating based on k-CA/AgNPs composite can achieve more than twice the silver loading on the fabric surface compared to the textile subjected to direct AgNPs incorporation. Furthermore, silver release tests in water showed that higher Ag⁺ levels were reached for k-CA/AgNPs-coated cotton. Therefore, inoculation tests with the bacteria Staphylococcus aureus (SA) using the agar diffusion method showed that samples covered with the composite resulted in significantly larger inhibition halos. This indicated that the use of the composite as a coating for cotton fabric improved its bactericidal activity against SA.

Here we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12Cwith a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding growth of insensitive cell clones, and proliferation. Statistics confirm the expectation that most resistance-related mutations are in cis, pointing to the high probability of cooperative, same-allele effects. In addition to targeted Ras inhibitors and drug combinations, bifunctional molecules and innovative tri-complex inhibitors to target Ras mutants are also under development. Since the identities and potential contributions of preexisting and evolving mutations are unknown, selecting a pharmacologic combination is taxing. Collectively, our broad review outlines considerations and provides new insights into pharmacology and resistance.