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The computational method has been proven to be a promising means for pre-screening large-scale anticancer drug combinations to support precision oncology applications. Pioneering efforts have been made to develop machine learning technology for predicting drug synergy, but high computational cost for training models as well as great diversity and limited size in screening data escalate the difficulty of prediction. To address this challenge, we propose a simple machine learning framework, namely Similarity Network-based Synergy prediction (SNSynergy), for predicting synergistic effects towards new cell lines and new drug combinations by two locally weighted models CLSN and DCSN. This framework only requires a small amount of auxiliary data, like genomics information of cell lines and the molecular fingerprints or targets of drugs. Based on the assumption that similar cell lines and similar drug combinations have similar synergistic effects, CLSN and DCSN predict synergy scores through capturing individual synergy contributions of nearest cell line and drug combination neighbors, respectively. High correlations between predicted and measured synergy scores on two leading cancer cell line pharmacogenomic screening datasets (the O'Neil dataset and the NCI-ALMANAC dataset) demonstrate the effectiveness and robustness of SNSynergy. Many of the identified drug combinations are consistent with previous studies, or have been explored in clinical settings against the specific cancer type, showing that SNSynergy has the potential to supply cost-saving and effective high-throughput screening for prioritizing the most applicable cell lines and the most promising drug combinations., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As a naturally occurring cytolytic peptide, melittin (MLT) not only exhibits a potent direct tumor cell-killing effect but also possesses various immunomodulatory functions. MLT shows minimal chances for developing resistance and has been recognized as a promising broad-spectrum antitumor drug because of this unique dual mechanism of action. However, MLT still displays obvious toxic side effects during treatment, such as nonspecific cytolytic activity, hemolytic toxicity, coagulation disorders, and allergic reactions, seriously hampering its broad clinical applications. With thorough research on antitumor mechanisms and the rapid development of nanotechnology, significant effort has been devoted to shielding against toxicity and achieving tumor-directed drug delivery to improve the therapeutic efficacy of MLT. Herein, we mainly summarize the potential antitumor mechanisms of MLT and recent progress in the targeted delivery strategies for tumor therapy, such as passive targeting, active targeting and stimulus-responsive targeting. Additionally, we also highlight the prospects and challenges of realizing the full potential of MLT in the field of tumor therapy. By exploring the antitumor molecular mechanisms and delivery strategies of MLT, this comprehensive review may inspire new ideas for tumor multimechanism synergistic therapy., (© 2023. The Author(s).)

Androgen deprivation in cases of castration-resistant prostate cancer (CRPC) leads to adverse effects, including loss of muscle and bone mass and gain of subcutaneous fat. The tumor-specific suppression of androgen receptor (AR) signaling, while not global, may reduce side effects. We present a class of small-molecular conjugates consisting of an AR antagonist linked to a heat shock protein 90 (Hsp90) inhibitor. We demonstrate that the high accumulation of Hsp90 on the surface of CRPC cells allows uptake of conjugates and increases the enrichment of drugs in the tumor cells. After penetrating prostate cancer cells, the conjugates not only inhibit AR function by the antagonist component but also bind to Hsp90 and suppress the AR protein level. Compared to AR antagonists, these conjugates showed improved tumor-targeting ability and enhanced potency against Enzalutamide-resistant 22Rv1 cells.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal disease with few treatment options. Steroid receptor coactivator-3 (SRC-3, also known as NCOA3, AIB1, pCIP, ACTR, RAC3, TRAM1) sits at the nexus of many growth signaling pathways and has been pursued as a therapeutic target for breast, prostate and lung cancers. In this study, we find that SRC-3 is overexpressed in PDAC and inversely correlates with patient overall survival. Knockdown of SRC-3 reduces pancreatic cancer cell proliferation, migration and invasion in vitro. Additionally, inhibition of SRC-3 using either shRNA or a small molecule inhibitor can significantly inhibit tumor growth in orthotopic pancreatic cancer mouse models. Collectively, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cisplatin is widely used in cancer treatment, but the application is limited due to toxicities and its acquired resistance. In this study, we delivered cisplatin to prostate cancer cells by linking the platinum prodrug Pt(IV) to melanin-like nanoparticles (MeNPs), a promising photothermal therapeutic agent with excellent biocompatibility. As expected, the Pt(IV)-MeNPs exhibited brilliant synergic photothermal-chemotherapy upon near-infrared reflection exposure. Compared with free cisplatin, Pt(IV)-MeNPs displayed highly effective antitumour activity both in vitro and in vivo.

In the past decade, monoclonal antibodies (mAbs) have revolutionized the treatment of non-Hodgkin lymphomas (NHLs). Although Fc-dependent mechanisms of mAb-mediated tumor clearance have been extensively studied, the ability of mAbs to directly evoke programmed cell death (PCD) and the underlying mechanisms involved remain unclear. It is well established that type II anti-CD20 mAb (Tositumomab) potently evoked PCD through a caspases-independent, lysosome-mediated process, which is related to homotypic adhesion (HA) in NHL cell lines. Herein, we reveal that the induction of ceramide generation by anti-CD20 mAbs directly correlates with their ability to induce PCD. The inhibition of ceramide abrogated Tositumomab-induced PCD indicating that ceramide is required for the execution of cell death. Further experimental results revealed that ceramide was generated downstream of mAb-induced HA and upstream of lysosome leakage. These findings provide further insights into a previously unrecognized role for ceramide generation in mediating PCD evoked by type II anti-CD20 mAbs in Burkitt's lymphoma cells. This newly characterized cell death pathway may potentially be exploited to eliminate malignant cells., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective. To prospectively study the application effect of traditional Chinese medicine (TCM) anticancer decoction with basic chemotherapy and nursing intervention on oral cancer patients after surgery and the effect on tumor markers and immune function. Methods. Eighty-four postoperative oral cancer patients in our hospital from May 2017 to February 2019 were selected and divided into observation group (42 cases) and control group (42 cases). The control group was treated with basic chemotherapy combined with basic nursing care, and the observation group was treated with TCM anticancer decoction and comprehensive nursing intervention on the basis of the control group. The clinical efficacy, the occurrence of adverse reactions, the satisfaction of nursing care, and the two-year cumulative survival rate of the two groups were compared. The immune function, tumor marker level, VAS score, QoR40 score, and survival quality score of the two groups were compared before and after nursing care. Results. The total clinical treatment efficiency of the observation group (88.10%) was significantly higher than that of the control group (69.05%), and the differences between the two groups in oral cleanliness, aspiration frequency, and oral comfort were statistically significant (P < 0.05). The differences in the occurrence of halitosis, oral fungal infection, leukopenia, gastrointestinal reaction, and fever in the observation group were statistically significant compared with the control group (P < 0.05). The nursing satisfaction rate in the observation group (95.24%) was significantly higher than that in the control group (78.57%). The two-year cumulative survival rate of the observation group (92.86%) was significantly higher than that of the control group (73.81%). After nursing care, CD4+, CD4+/CD8+, VAS scores, QoR40 scores, and quality of survival scores in both groups all increased, and CD8+, CD56+, CEA level, NSE level, and CA19-9 level all decreased (all P < 0.05). Conclusion. The clinical efficacy of TCM anticancer decoction with basic chemotherapy and nursing interventions in the treatment of postoperative oral cancer patients was remarkable, which could significantly improve patients' oral cleanliness and comfort, reduce the frequency of sputum aspiration, improve patients' immunity, reduce tumor marker levels, inhibit tumor activity, improve patients' nursing satisfaction, further improve patients' treatment compliance, reduce patients' pain level, improve patients' survival quality, and prolong patients' survival time with high safety. It could be used as a theoretical basis for subsequent clinical research. [ABSTRACT FROM AUTHOR]