-
Cancer Letters May 2023Cancer immunotherapies have yielded promising outcomes in various malignant tumors by blocking specific immune checkpoint molecules, such as programmed cell death 1 and... (Review)
Review
Cancer immunotherapies have yielded promising outcomes in various malignant tumors by blocking specific immune checkpoint molecules, such as programmed cell death 1 and cytotoxic T lymphocyte antigen 4. However, only a few patients respond to immune checkpoint blockade therapy because of the poor immunogenicity of tumor cells and immune-suppressive tumor microenvironment. Accumulating evidence suggests that chemotherapeutic agents, including oxaliplatin and doxorubicin, not only mediate direct cytotoxicity in tumor cells but also induce immunogenic cancer cell death to stimulate a powerful anti-cancer immune response in the tumor microenvironment. In this review, we summarize the recent advances in cancer combination therapy based on immune checkpoint inhibitors plus immunogenic cell death inducers. Despite some clinical failures and challenges, immunogenic cell death inducers have displayed great potential when combined with immune checkpoint inhibitors for anti-cancer treatment in both preclinical studies and clinical trials.
Topics: Humans; Immune Checkpoint Inhibitors; Immunogenic Cell Death; Antineoplastic Agents; Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 37031916
DOI: 10.1016/j.canlet.2023.216167 -
Cancer Treatment and Research... 2021With the development of trastuzumab for metastatic breast cancer a new era began in cancer drug development. The drug-diagnostic codevelopment model with its clinical...
With the development of trastuzumab for metastatic breast cancer a new era began in cancer drug development. The drug-diagnostic codevelopment model with its clinical enrichment trial design has enabled development of target specific drugs for molecular defined subsets of patients. Since the simultaneous approval of trastuzumab and the HercepTest in 1998, the number of FDA-approved drug-companion diagnostic combinations within oncology and hematology have steadily increased. By June 2021, the number of drugs that have a companion diagnostic (CDx) linked to its use has reached 46. For these drugs, the CDx assays play an important role in defining the patient population likely to respond and without the assay they will often lose their value. This short article is based on an analysis of the FDA List of Cleared or Approved Companion Diagnostic Devices and relevant information in the Drugs@FDA, and will focus on the drug-CDx combinations, drug classes, clinical development, and the regulatory path and status.
Topics: Antineoplastic Agents; Humans; Medical Oncology; Neoplasms
PubMed: 34844911
DOI: 10.1016/j.ctarc.2021.100492 -
Frontiers in Immunology 2022Commensal bacteria and other microorganisms that reside in the human body are closely associated with the development and treatment of cancers. Recently, tumor... (Review)
Review
Commensal bacteria and other microorganisms that reside in the human body are closely associated with the development and treatment of cancers. Recently, tumor microbiome (TM) has been identified in a variety of cancers such as pancreatic, lung, and breast cancers. TM has different compositions in different tumors and has different effects on tumors. TM plays an important role in the formation of the tumor microenvironment, regulation of local immunity, and modification of tumor cell biology, and directly affects the efficacy of drug treatment for tumors. TM is expected to be a biomarker for tumors, and engineered tumor-targeting bacteria and anti-cancer microbial agents (GEN-001) have an important role in the treatment of tumors. This paper reviews the relevant studies on TM in recent years and describes its distribution in different tumors, its correlation with clinical features, its effect on local immunity, and the research directions of TM in tumor treatment.
Topics: Antineoplastic Agents; Bacteria; Breast Neoplasms; Female; Humans; Immunotherapy; Microbiota; Tumor Microenvironment
PubMed: 35911695
DOI: 10.3389/fimmu.2022.935846 -
European Journal of Pharmaceutical... Jan 2023In the current investigation, fifteen novel imidazole-pyridine-based molecules were synthesized and tested against cell lines of the lung (H1299) and colon (HCT116)...
In the current investigation, fifteen novel imidazole-pyridine-based molecules were synthesized and tested against cell lines of the lung (H1299) and colon (HCT116) adenocarcinomas by proliferation assay. The results demonstrated that compounds 5a, 5d, 5e, and 5f were the most active (IC<30 µM). Based on recent literature and the current results, the glycogen synthase kinase-3β (GSK-3β) protein was investigated in-silico as a possible target. The molecular docking and QSAR revealed an excellent binding affinity of the selected imidazole-pyridine compounds to GSK-3β. Notably, GSK-3β protein levels were significantly upregulated in hepatocellular liver carcinoma (LIHCs) tissues and negatively affected patient prognosis. Consequently, the compounds were evaluated on liver cancer cell lines (HepG2, HUH-7, and PLC/PRF/5) by the MTT assay, and 5d showed the highest antitumor activity. This study offers new compounds with interesting biological activity on GSK-3β as a target, exhibiting a potential therapeutic impact for hepatocellular carcinoma patients.
Topics: Humans; Glycogen Synthase Kinase 3 beta; Molecular Docking Simulation; Carcinoma, Hepatocellular; Antineoplastic Agents; Liver Neoplasms
PubMed: 36336277
DOI: 10.1016/j.ejps.2022.106323 -
Zhongguo Fei Ai Za Zhi = Chinese... Jun 2022DNA damage repair (DDR) system plays an important role in maintaining of genomic stability. Accumulation of DNA lesions or deficiency of DDR system could drive... (Review)
Review
DNA damage repair (DDR) system plays an important role in maintaining of genomic stability. Accumulation of DNA lesions or deficiency of DDR system could drive tumorigenesis as well as promote tumor progression; meanwhile, they could also provide therapeutic opportunities and targets. Of all the antineoplastic agents of lung cancers, many of them targeted or were associated with DNA damage and repair pathways, such as chemotherapies and antibody-drug conjugates which were designed directly causing DNA damages, targeted drugs inhibiting DNA repair pathways, and immune-checkpoint inhibitors. In this review, we described the role of DNA damage and repair pathways in antitumor activity of the above agents, as well as summarized the application and clinical investigations of these antineoplastic agents in lung cancers, in order to provide more information for exploring precision and effective strategies for the treatment of lung cancer based on the mechanism of DNA damage and repair. .
Topics: Antineoplastic Agents; DNA Damage; DNA Repair; Humans; Lung Neoplasms; Neoplasms
PubMed: 35747923
DOI: 10.3779/j.issn.1009-3419.2022.101.24 -
Biochimie Nov 2022Since the early discovery of plant lectins at the end of the 19th century, and the finding that they could agglutinate erythrocytes and precipitate glycans from their... (Review)
Review
Since the early discovery of plant lectins at the end of the 19th century, and the finding that they could agglutinate erythrocytes and precipitate glycans from their solutions, many applications and biological roles have been described for these proteins. Later, the observed erythrocytes clumping features were attributed to the lectin-cell surface glycoconjugates recognition. Neoplastic transformation leads to various cellular alterations which impact the growth of the cell and its persistence, among which is the mutation in the outer surface glycosylation signatures. Quite a few lectins have been found to act as excellent biomarkers for cancer diagnosis while some were presented with antiproliferative activity that initiated by lectin binding to the respective glycocalyx receptors. These properties are blocked by the hapten sugar that is competing for the lectin affinity binding site. In vitro investigations of lectin-cancer cell's glycocalyx interactions lead to a series of immunological reactions that result in autophagy or apoptosis of the transformed cells. Mistletoe lectin, an agglutinin purified from the European Viscum album is the first plant lectin employed in the treatment of cancer to enter into the clinical trial phases. The entrapment of lectin in nanoparticles besides other techniques to promote bioavailability and stability have also been recently studied. This review summarizes our up-to-date understanding of the future applications of plant lectins in cancer prognosis and diagnosis. With the provision of many examples of lectins that exhibit anti-neoplastic properties.
Topics: Plant Lectins; Antineoplastic Agents; Lectins; Apoptosis; Biological Products
PubMed: 35952948
DOI: 10.1016/j.biochi.2022.08.002 -
Journal of Medicinal Chemistry Jul 2022Glioblastoma (GBM) is a highly malignant brain tumor characterized by a heterogeneous population of genetically unstable and highly infiltrative cells that are resistant... (Review)
Review
Glioblastoma (GBM) is a highly malignant brain tumor characterized by a heterogeneous population of genetically unstable and highly infiltrative cells that are resistant to chemotherapy. Although substantial efforts have been invested in the field of anti-GBM drug discovery in the past decade, success has primarily been confined to the preclinical level, and clinical studies have often been hampered due to efficacy-, selectivity-, or physicochemical property-related issues. Thus, expansion of the list of molecular targets coupled with a pragmatic design of new small-molecule inhibitors with central nervous system (CNS)-penetrating ability is required to steer the wheels of anti-GBM drug discovery endeavors. This Perspective presents various aspects of drug discovery (challenges in GBM drug discovery and delivery, therapeutic targets, and agents under clinical investigation). The comprehensively covered sections include the recent medicinal chemistry campaigns embarked upon to validate the potential of numerous enzymes/proteins/receptors as therapeutic targets in GBM.
Topics: Antineoplastic Agents; Brain Neoplasms; Drug Discovery; Glioblastoma; Humans
PubMed: 35786935
DOI: 10.1021/acs.jmedchem.1c01946 -
Marine Drugs Dec 2019In 2019, the scientific and medical community celebrated the 50th anniversary of the introduction of the very first marine-derived drug, Cytarabine, into clinics [...].
In 2019, the scientific and medical community celebrated the 50th anniversary of the introduction of the very first marine-derived drug, Cytarabine, into clinics [...].
Topics: Animals; Antineoplastic Agents; Aquatic Organisms; History, 21st Century; Humans; Neoplasms
PubMed: 31887976
DOI: 10.3390/md18010020 -
Biomolecules May 2020The blooming of nanotechnology has made available a limitless landscape of solutions responding to crucial issues in many fields and, nowadays, a wide choice of... (Review)
Review
The blooming of nanotechnology has made available a limitless landscape of solutions responding to crucial issues in many fields and, nowadays, a wide choice of nanotechnology-based strategies can be adopted to circumvent the limitations of conventional therapies for cancer. Herein, the current stage of nanotechnological applications for cancer management is summarized encompassing the core nanomaterials as well as the available chemical-physical approaches for their surface functionalization and drug ligands as possible therapeutic agents. The use of nanomaterials as vehicles to delivery various therapeutic substances is reported emphasizing advantages, such as the high drug loading, the enhancement of the pay-load half-life and bioavailability. Particular attention was dedicated to highlight the importance of nanomaterial intrinsic features. Indeed, the ability of combining the properties of the transported drug with the ones of the nano-sized carrier can lead to multifunctional theranostic tools. In this view, fluorescence of carbon quantum dots, optical properties of gold nanoparticle and superparamagnetism of iron oxide nanoparticles, are fundamental examples. Furthermore, smart anticancer devices can be developed by conjugating enzymes to nanoparticles, as in the case of bovine serum amine oxidase (BSAO) and gold nanoparticles. The present review is aimed at providing an overall vision on nanotechnological strategies to face the threat of human cancer, comprising opportunities and challenges.
Topics: Adsorption; Animals; Antineoplastic Agents; Biomedical Technology; Humans; Nanoparticles; Nanotechnology
PubMed: 32397196
DOI: 10.3390/biom10050735 -
Pharmacological Research May 2024Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, and mortality, highlighting the necessity for... (Review)
Review
Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, and mortality, highlighting the necessity for transformative treatment approaches. Photodynamic therapy (PDT) has aroused continuous interest as a viable alternative to conventional cancer treatments that encounter drug resistance. Nanotechnology has brought new advances in medicine and has shown great potential in drug delivery and cancer treatment. For precise and efficient therapeutic utilization of such a tumor therapeutic approach with high spatiotemporal selectivity and minimal invasiveness, the carrier-free noncovalent nanoparticles (NPs) based on chemo-photodynamic combination therapy is essential. Utilizing natural products as the foundation for nanodrug development offers unparalleled advantages, including exceptional pharmacological activity, easy functionalization/modification, and well biocompatibility. The natural-product-based, carrier-free, noncovalent NPs revealed excellent synergistic anticancer activity in comparison with free photosensitizers and free bioactive natural products, representing an alternative and favorable combination therapeutic avenue to improve therapeutic efficacy. Herein, a comprehensive summary of current strategies and representative application examples of carrier-free noncovalent NPs in the past decade based on natural products (such as paclitaxel, 10-hydroxycamptothecin, doxorubicin, etoposide, combretastatin A4, epigallocatechin gallate, and curcumin) for tumor chemo-photodynamic combination therapy. We highlight the insightful design and synthesis of the smart carrier-free NPs that aim to enhance PDT efficacy. Meanwhile, we discuss the future challenges and potential opportunities associated with these NPs to provide new enlightenment, spur innovative ideas, and facilitate PDT-mediated clinical transformation.
Topics: Humans; Photochemotherapy; Animals; Neoplasms; Nanoparticles; Biological Products; Antineoplastic Agents; Photosensitizing Agents
PubMed: 38521285
DOI: 10.1016/j.phrs.2024.107150