Combination therapy can greatly improve the efficacy of cancer treatment, so identifying the most effective drug combination and interaction can accelerate the development of combination therapy. Here we developed a computational network biological approach to identify the effective drug which inhibition risk pathway crosstalk of cancer, and then filtrated and optimized the drug combination for cancer treatment. We integrated high-throughput data concerning pan-cancer and drugs to construct miRNA-mediated crosstalk networks among cancer pathways and further construct networks for therapeutic drug. Screening by drug combination method, we obtained 687 optimized drug combinations of 83 first-line anticancer drugs in pan-cancer. Next, we analyzed drug combination mechanism, and confirmed that the targets of cancer-specific crosstalk network in drug combination were closely related to cancer prognosis by survival analysis. Finally, we save all the results to a webpage for query ( http://bio-bigdata.hrbmu.edu.cn/oDrugCP/ ). In conclusion, our study provided an effective method for screening precise drug combinations for various cancer treatments, which may have important scientific significance and clinical application value for tumor treatment.
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http://dx.doi.org/10.1038/s41597-024-02915-y | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Combination therapies using checkpoint inhibitors with immunostimulatory agonists have attracted great attention due to their synergistic therapeutic effects for cancer treatment. However, such combination immunotherapies require specific timing of doses to show sufficient antitumor efficacy. Sequential treatment usually requires multiple administrations of the individual drugs at specific time points, thus increasing the complexity of the drug regimen and compromising patient compliance.
View Article and Find Full Text PDFJ Pharm Pharmacol
January 2025
Department of Cell Biology, School of Life Sciences, Central South University; Changsha, Hunan, 410013, P.R. China.
Objectives: Pancreatic cancer, a highly invasive and prognostically unfavorable malignant tumor, consistently exhibits resistance to conventional chemotherapy, leading to substantial side effects and diminished patient quality of life. This highlights the critical need for the discovery of novel, effective, and safe chemotherapy drugs. This study aimed to explore bioactive compounds, particularly natural products, as an alternative for JAK2 protein inhibitor in cancer treatment.
View Article and Find Full Text PDFJ Med Chem
January 2025
Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Based on our previous work, a series of imidazole-based small molecules were designed and synthesized as HDAC3 inhibitors. Among them, compound showed selective HDAC3 inhibition activity with an IC of 53 nM (SI = 75 for HDAC3 over HDAC1). Further studies revealed that could dose-dependently induce the expression of PD-L1 in MC38 cells by activating the PD-L1 transcription.
View Article and Find Full Text PDFArch Orthop Trauma Surg
January 2025
Department of Anaesthesia, Main-Kinzig-Kliniken, Herzbachweg 14, 63571, Gelnhausen, Germany.
Background: Total knee arthroplasty (TKA) is associated with moderate to severe postoperative pain. Pain control is crucial for rapid mobilisation and reduces side effects as well as the length of hospital stay. In this context, a variety of multimodal pain control regimes show good pain relief, including several nerve blocks, iPACK and local infiltration analgesia (LIA).
View Article and Find Full Text PDFAm J Cardiovasc Drugs
January 2025
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Oral bempedoic acid (NEXLETOL in the USA; Nilemdo in the EU) and the fixed dose combination (FDC) of bempedoic acid/ezetimibe (NEXLIZET in the USA; Nustendi in the EU) are approved to reduce cardiovascular (CV) risk in statin-intolerant patients who are at high risk for, or have, CV disease. A first-in-class therapy, bempedoic acid inhibits the adenosine triphosphate-citrate lyase enzyme in the cholesterol biosynthesis pathway. In the multinational phase III CLEAR Outcomes trial in statin-intolerant patients, once-daily bempedoic acid 180 mg significantly reduced the risk of the primary endpoint (a four-component major adverse CV event composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) compared with placebo.
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