Search

Targeting androgen receptor (AR) has shown great therapeutic potential in triple-negative breast cancer (TNBC), yet its efficacy remains unsatisfactory. Here, we aimed to identify promising targeted agents that synergize with enzalutamide, a second-generation AR inhibitor, in TNBC. By using a strategy for screening drug combinations based on the Sensitivity Index (SI), we found that MK-8776, a selective checkpoint kinase1 (CHK1) inhibitor, showed favorable synergism with enzalutamide in AR-positive TNBC. The combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776, respectively. Furthermore, a nanoparticle-based on hyaluronic acid (HA)-modified hollow-manganese dioxide (HMnO 2 ), named HMnE&M@H, was established to encapsulate and deliver enzalutamide and MK-8776. This HA-modified nanosystem managed targeted activation via pH/glutathione responsiveness. HMnE&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a carrier. Collectively, our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H, providing a potential therapeutic approach for the treatment of TNBC., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

Reprogramming of the tumor microenvironment (TME) is a hallmark of cancer. Metabolic reprogramming is a vital approach to sustaining the energy supply in the TME. This alteration exists in both cancer cells and TME cells, collectively establishing an immunotolerant niche to facilitate tumor progression. Limited resources lead to metabolic competition and hinder the biological functions of anti-tumoral immunity. Reprogramming of lipid metabolism and tumor progression is closely related to each other. Due to the complexity of fatty acid (FA) types and the lack of an effective approach for detection, the mechanisms and effects of FA metabolic reprogramming have been unclear. Herein, we review FA metabolism in the tumor milieu, summarize how FA metabolic reprogramming influences antitumor immune response, suggest the mechanisms by which FAs affect immunotherapy against cancer, and discuss the potential of FA metabolism-based drugs in cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

A new type of temperature-sensitive imprinted composite membranes(ICMs) was developed. Poly N,N-diethylacrylamide (DEA) blocks, as temperature-sensitive polymer, were grafted onto the substrate of the imprinted polymer separation layer to endow membranes with better adsorption effect. The comprehensive properties of the imprinted composite membranes were adequately tested and evaluated in detail. Results showed that ReO 4 - -ICMs (Re-ICMs) with temperature-sensitive recognition sites could adjust the structure of the imprinted holes at different temperatures, which presented excellent performance in the selective separation and purification of ReO 4 - . The prepared Re-ICMs exhibit the maximum adsorption capacity of 0.1639 mmol/g at 35 °C with the equilibrium adsorption time of 2 h. After ten adsorption/desorption cycles, Re-ICMs could still maintain 73.5% of the original adsorption capacity, the separation degree of ReO 4 - /MnO 4 - was only reduced from the initial 24.5 to 15.9, and the desorption ratio dropped from 80.4% to 68.4%, indicating that Re-ICMs have excellent adsorption and separation performance and reusability., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The formation of cyclinD-CDK4/6 complex plays vital roles in the cell cycle transition from G1 phase to S phase which is characterized by vigorous transcription and synthesis. Through cyclinD-CDK4/6-Rb axis, CDK4/6 inhibitors arrest the cell cycle in the G1 phase and block the proliferation of aggressive cells, exhibiting promising effects in containing the aggressiveness of breast cancers. To date, there are three CDK4/6 inhibitors approved by the U.S. Food and Drug Administration in treating advanced hormone receptor-positive breast cancer, including palbociclib, abemaciclib, and ribociclib. In fact, several preclinical experiments and clinical trials presented therapeutic effects of CDK4/6 inhibitor-based treatment in triple-negative breast cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)