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International Journal of Molecular... Feb 2024Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in... (Review)
Review
Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Mevalonic Acid; Prostatic Neoplasms; Receptors, Androgen; Antineoplastic Agents
PubMed: 38396837
DOI: 10.3390/ijms25042152 -
International Journal of Molecular... Nov 2023Nature has always been a precious source of bioactive molecules which are used for the treatment of various diseases [...].
Nature has always been a precious source of bioactive molecules which are used for the treatment of various diseases [...].
Topics: Humans; Neoplasms; Biological Products; Antineoplastic Agents
PubMed: 38003697
DOI: 10.3390/ijms242216507 -
Farmacia Hospitalaria : Organo Oficial... 2024
Topics: Humans; Precision Medicine; Hematologic Neoplasms; Pharmaceutical Services; Antineoplastic Agents
PubMed: 38705827
DOI: 10.1016/j.farma.2024.04.002 -
Scientific Reports Jul 2023Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can...
Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased apoptosis, which was confirmed by using an Annexin-V/PI assay. Interestingly, NSC260594 treatment reduced the cancer stem cell (CSC) population in TNBCs. To make NSC260594 more clinically relevant, we treated NSC260594 with TNBC cell derived xenograft (CDX) mouse model, and with patient-derived xenograft (PDX) organoids. NSC260594 significantly suppressed MDA-MB-231 tumor growth in vivo, and furthermore, the combination treatment of NSC260594 and everolimus acted synergistically to decrease growth of TNBC PDX organoids. Together, we found that NSC260594 might serve as a lead compound for triple-negative breast cancer therapy through targeting Mcl-1.
Topics: Animals; Humans; Mice; Annexin A5; Antibodies; Antineoplastic Agents; Disease Models, Animal; Triple Negative Breast Neoplasms
PubMed: 37481672
DOI: 10.1038/s41598-023-37058-4 -
Advanced Science (Weinheim,... Sep 2023The gut microbiome plays a crucial role in modulating host health and disease. It serves as a vast reservoir of functional molecules that hold great potential for...
The gut microbiome plays a crucial role in modulating host health and disease. It serves as a vast reservoir of functional molecules that hold great potential for clinical applications. One specific area of interest is identifying anticancer peptides (ACPs) for innovative cancer therapies. However, ACPs discovery is hindered by a heavy reliance on experimental methodologies. To overcome this limitation, we here employed a novel approach by leveraging the overlap between ACPs and antimicrobial peptides (AMPs). By combining well-established AMP prediction methods with mining techniques in metagenomic cohorts, a total of 40 potential ACPs is identified. Out of the identified ACPs, 39 demonstrated inhibitory effects against at least one cancer cell line, exhibiting significant differences from known ACPs. Moreover, the therapeutic potential of the two most promising peptides in a mouse xenograft cancer model is evaluated. Encouragingly, the peptides exhibit effective tumor inhibition without any detectable toxic effects. Interestingly, both peptides display uncommon secondary structures, highlighting its distinctive characteristics. This findings highlight the efficacy of the multi-center mining approach, which effectively uncovers novel ACPs from the gut microbiome. This approach has significant implications for expanding treatment options not only for CRC, but also for other cancer types.
Topics: Humans; Animals; Mice; Antineoplastic Agents; Metagenome; Peptides; Neoplasms; Cell Line
PubMed: 37382183
DOI: 10.1002/advs.202300107 -
Biochemical Pharmacology Sep 2023Nucleoside-based drugs, recognized as purine or pyrimidine analogs, have been potent therapeutic agents since their introduction in 1950, deployed widely in the... (Review)
Review
Nucleoside-based drugs, recognized as purine or pyrimidine analogs, have been potent therapeutic agents since their introduction in 1950, deployed widely in the treatment of diverse diseases such as cancers, myelodysplastic syndromes, multiple sclerosis, and viral infections. These antimetabolites establish complex interactions with cellular molecular constituents, primarily via activation of phosphorylation cascades leading to consequential interactions with nucleic acids. However, the therapeutic efficacy of these agents is frequently compromised by the development of drug resistance, a continually emerging challenge in their clinical application. This comprehensive review explores the mechanisms of resistance to nucleoside-based drugs, encompassing a wide spectrum of phenomena from alterations in membrane transporters and activating kinases to changes in drug elimination strategies and DNA damage repair mechanisms. The critical analysis in this review underlines complex interactions of drug and cell and also guides towards novel therapeutic strategies to counteract resistance. The development of targeted therapies, novel nucleoside analogs, and synergistic drug combinations are promising approaches to restore tumor sensitivity and improve patient outcomes.
Topics: Humans; Nucleosides; Antineoplastic Agents; Neoplasms; Drug Resistance; Membrane Transport Proteins; Antimetabolites
PubMed: 37567317
DOI: 10.1016/j.bcp.2023.115741 -
International Journal of Molecular... Nov 2023Gastrointestinal cancer is a common clinical malignant tumor disease that seriously endangers human health and lacks effective treatment methods. As part of the innate... (Review)
Review
Gastrointestinal cancer is a common clinical malignant tumor disease that seriously endangers human health and lacks effective treatment methods. As part of the innate immune defense of many organisms, antimicrobial peptides not only have broad-spectrum antibacterial activity but also can specifically kill tumor cells. The positive charge of antimicrobial peptides under neutral conditions determines their high selectivity to tumor cells. In addition, antimicrobial peptides also have unique anticancer mechanisms, such as inducing apoptosis, autophagy, cell cycle arrest, membrane destruction, and inhibition of metastasis, which highlights the low drug resistance and high specificity of antimicrobial peptides. In this review, we summarize the related studies on antimicrobial peptides in the treatment of digestive tract tumors, mainly oral cancer, esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer. This paper describes the therapeutic advantages of antimicrobial peptides due to their unique anticancer mechanisms. The length, net charge, and secondary structure of antimicrobial peptides can be modified by design or modification to further enhance their anticancer effects. In summary, as an emerging cancer treatment drug, antimicrobial peptides need to be further studied to realize their application in gastrointestinal cancer diseases.
Topics: Humans; Antimicrobial Peptides; Antimicrobial Cationic Peptides; Gastrointestinal Neoplasms; Antineoplastic Agents; Stomach Neoplasms; Anti-Bacterial Agents
PubMed: 38069041
DOI: 10.3390/ijms242316718 -
Bioorganic Chemistry Jul 2023Small molecule theranostic agents for tumor treatment exhibited triadic properties in tumor targeting, imaging, and therapy, which have attracted increasing attention as... (Review)
Review
Small molecule theranostic agents for tumor treatment exhibited triadic properties in tumor targeting, imaging, and therapy, which have attracted increasing attention as a potential complement for, or improved to, classical small molecule antitumor drugs. Photosensitizer have dual functions of imaging and phototherapy, and have been widely used in the construction of small molecule theranostic agents over the last decade. In this review, we summarized representative agents that have been studied in the field of small molecule theranostic agents based on photosensitizer in the last decade, and highlighted their characteristics and application in tumor-targeted monitoring and phototherapy. The challenges and future perspectives of photosensitizers in building small molecule theranostic agents for diagnosis and therapy of tumors were also discussed.
Topics: Humans; Photosensitizing Agents; Precision Medicine; Phototherapy; Neoplasms; Antineoplastic Agents; Nanoparticles; Cell Line, Tumor
PubMed: 37094481
DOI: 10.1016/j.bioorg.2023.106554 -
Molecules (Basel, Switzerland) May 2024Cancer is ranked among lethal diseases globally, and the increasing number of cancer cases and deaths results from limited access to effective therapeutics. The use of... (Review)
Review
Cancer is ranked among lethal diseases globally, and the increasing number of cancer cases and deaths results from limited access to effective therapeutics. The use of plant-based medicine has been gaining interest from several researchers. Carvacrol and its isomeric compound, thymol, are plant-based extracts that possess several biological activities, such as antimalarial, anticancer, antifungal, and antibacterial. However, their efficacy is compromised by their poor bioavailability. Thus, medicinal scientists have explored the synthesis of hybrid compounds containing their pharmacophores to enhance their therapeutic efficacy and improve their bioavailability. Hence, this review is a comprehensive report on hybrid compounds containing carvacrol and its isomer, thymol, with potent anticancer and antibacterial agents reported between 2020 and 2024. Furthermore, their structural activity relationship (SAR) and recommended future strategies to further enhance their therapeutic effects will be discussed.
Topics: Thymol; Cymenes; Humans; Anti-Bacterial Agents; Antineoplastic Agents; Structure-Activity Relationship; Neoplasms; Animals
PubMed: 38792138
DOI: 10.3390/molecules29102277 -
Pharmacological Research Aug 2023Drug combination therapy is a highly effective approach for enhancing the therapeutic efficacy of anti-cancer drugs and overcoming drug resistance. However, the... (Review)
Review
Drug combination therapy is a highly effective approach for enhancing the therapeutic efficacy of anti-cancer drugs and overcoming drug resistance. However, the innumerable possible drug combinations make it impractical to screen all synergistic drug pairs. Moreover, biological insights into synergistic drug pairs are still lacking. To address this challenge, we systematically analyzed drug combination datasets curated from multiple databases to identify drug pairs more likely to show synergy. We classified drug pairs based on their MoA and discovered that 110 MoA pairs were significantly enriched in synergy in at least one type of cancer. To improve the accuracy of predicting synergistic effects of drug pairs, we developed a suite of machine learning models that achieve better predictive performance. Unlike most previous methods that were rarely validated by wet-lab experiments, our models were validated using two-dimensional cell lines and three-dimensional tumor slice culture (3D-TSC) models, implying their practical utility. Our prediction and validation results indicated that the combination of the RTK inhibitors Lapatinib and Pazopanib exhibited a strong therapeutic effect in breast cancer by blocking the downstream PI3K/AKT/mTOR signaling pathway. Furthermore, we incorporated molecular features to identify potential biomarkers for synergistic drug pairs, and almost all potential biomarkers found connections between drug targets and corresponding molecular features using protein-protein interaction network. Overall, this study provides valuable insights to complement and guide rational efforts to develop drug combination treatments.
Topics: Humans; Female; Phosphatidylinositol 3-Kinases; Antineoplastic Agents; Signal Transduction; Breast Neoplasms; Drug Delivery Systems
PubMed: 37343647
DOI: 10.1016/j.phrs.2023.106830