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Cancer Medicine Jul 2023Inhibitors of apoptosis proteins (IAPs) inhibit the intrinsic and extrinsic cell death pathways, promoting cell survival. Antagonists of these pathways are under study... (Review)
Review
Inhibitors of apoptosis proteins (IAPs) inhibit the intrinsic and extrinsic cell death pathways, promoting cell survival. Antagonists of these pathways are under study as anti-cancer therapeutics. A high proportion of head and neck squamous cell carcinomas (HNSCCs) have genomic alterations in IAP pathways, resulting in the dysregulation of cell death pathways and rendering them susceptible to IAP antagonist therapy. Preclinical studies suggest IAP antagonists, also known as second mitochondria-derived activator of caspases mimetics, may be effective treatments for HNSCC, especially when combined with radiation. Mechanistic studies have shown both molecular mechanisms (i.e., enhanced cell death) and immune mechanisms (e.g., immunogenic cell death and T-cell activation), underlying the efficacy of these drugs in preclinical models. Phase I/II clinical trials have shown promising results, portending a future where this class of targeted therapies becomes incorporated into the treatment paradigm for head and neck cancers. IAP antagonists have shown great promise for head and neck cancer, especially in combination with radiation therapy. Here, we review recent preclinical and clinical studies on the use of these novel targeted agents for head and neck cancer.
Topics: Humans; Inhibitor of Apoptosis Proteins; Apoptosis; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Cell Line, Tumor
PubMed: 37132167
DOI: 10.1002/cam4.6011 -
Anais Da Academia Brasileira de Ciencias 2023The aim of the present study was to perform in vitro and in vivo assessments of the antineoplastic action of 4-amino-pyrimidine encapsulated in liposomes. Liposomes were...
The aim of the present study was to perform in vitro and in vivo assessments of the antineoplastic action of 4-amino-pyrimidine encapsulated in liposomes. Liposomes were prepared and characterized for particle size and drug encapsulation and submitted to long-term stability tests. Cytotoxicity assays were performed in HeLa cells. Antineoplastic activity was investigated using the experimental sarcoma 180 tumor in Swiss albino mice. Encapsulation efficiency was 82.93 ± 0.04% and no significant changes were found with respect to particle size or pH after centrifugation and mechanical agitation tests. The in vitro results at concentration of 20 μg/mL indicated a considerable reduction in cell viability after treatment with encapsulated pyrimidine (75.91%). The in vivo assays using the compounds in encapsulated and free forms and 5-fluorouracil achieved tumor inhibition rates of 66.47 ± 26.8%, 50.46 ± 16.24% and 14.47 ± 9.22%, respectively. Mitotic counts demonstrated a greater reduction in the number of mitoses in animals treated with liposomal pyrimidine (32.15%) compared to those treated with the pyrimidine free (87.69%) and 5-fluorouracil (71.39%). This study demonstrated that the development of liposome formulations containing 4-amino-pyrimidine is a promising alternative for overcoming limitations related to the toxicity of current cancer treatment, ensuring greater therapeutic efficacy.
Topics: Mice; Humans; Animals; Liposomes; HeLa Cells; Antineoplastic Agents; Fluorouracil; Mitosis; Neoplasms
PubMed: 37436228
DOI: 10.1590/0001-3765202320211078 -
Journal of Nanobiotechnology Sep 2023Colorectal cancer (CRC) is a major cause of cancer-related deaths in humans, and effective treatments are still needed in clinical practice. Despite significant...
Colorectal cancer (CRC) is a major cause of cancer-related deaths in humans, and effective treatments are still needed in clinical practice. Despite significant developments in anticancer drugs and inhibitors, their poor stability, water solubility, and cellular membrane permeability limit their therapeutic efficacy. To address these issues, multifunctional CaCO nanoparticles loaded with Curcumin (Cur) and protein deacetylase (HDAC) inhibitor QTX125, and coated with hyaluronic acid (HA) (CaCO@Cur@QTX125@HA), were prepared through a one-step gas diffusion strategy. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) showed that CaCO@Cur@QTX125@HA nanoparticles have uniform spherical morphology and elemental distribution, with diameters around 450 nm and a Zeta potential of - 8.11 mV. The controlled release of Cur from the nanoparticles was observed over time periods of 48 h. Cellular uptake showed that CaCO@Cur@QTX125@HA nanoparticles were efficiently taken up by cancer cells and significantly inhibited their growth. Importantly, CaCO@Cur@QTX125@HA nanoparticles showed specific inhibitory effects on CRC cell growth. Encouragingly, CaCO@Cur@QTX125@HA nanoparticles successfully internalized into CRC patient-derived organoid (PDO) models and induced apoptosis of tumor cells. The multifunctional CaCO@Cur@QTX125@HA nanoparticles hold promise for the treatment of CRC.
Topics: Humans; Curcumin; Hyaluronic Acid; Antineoplastic Agents; Nanoparticles; Colorectal Neoplasms
PubMed: 37773145
DOI: 10.1186/s12951-023-02104-w -
Cancer Research and Treatment Jul 2023Cancer is a leading cause of disease-related mortality worldwide. Drug resistance is one of the primary reasons for the failure of anticancer therapy. There are a number... (Review)
Review
Cancer is a leading cause of disease-related mortality worldwide. Drug resistance is one of the primary reasons for the failure of anticancer therapy. There are a number of underlying mechanisms for anticancer drug resistance including genetic/epigenetic modifications, microenvironmental factors, and tumor heterogeneity. In the present scenario, researchers have focused on these novel mechanisms and strategies to tackle them. Recently, researchers have recognized the ability of cancer to become dormant because of anticancer drug resistance, tumor relapse, and progression. Currently, cancer dormancy is classified into "tumor mass dormancy" and "cellular dormancy." Tumor mass dormancy represents the equilibrium between cell proliferation and cell death under the control of blood supply and immune responses. Cellular dormancy denotes the state in which cells undergo quiescence and is characterized by autophagy, stress-tolerance signaling, microenvironmental cues, and epigenetic modifications. Cancer dormancy has been regarded as the stem of primary or distal recurrent tumor formation and poor clinical outcomes in cancer patients. Despite the insufficiency of reliable models of cellular dormancy, the mechanisms underlying the regulation of cellular dormancy have been clarified in numerous studies. A better understanding of the biology of cancer dormancy is critical for the development of effective anticancer therapeutic strategies. In this review, we summarize the characteristics and regulatory mechanisms of cellular dormancy, introduce several potential strategies for targeting cellular dormancy, and discuss future perspectives.
Topics: Humans; Neoplasm Recurrence, Local; Neoplasms; Cell Death; Signal Transduction; Autophagy; Antineoplastic Agents
PubMed: 36960624
DOI: 10.4143/crt.2023.468 -
International Immunopharmacology Sep 2023As a new group of anticancer drugs, immune checkpoint inhibitors (ICIs) have exhibited favorable antitumor efficacy in numerous malignant tumors. Anti-cytotoxic T... (Review)
Review
As a new group of anticancer drugs, immune checkpoint inhibitors (ICIs) have exhibited favorable antitumor efficacy in numerous malignant tumors. Anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) are three kinds of ICIs widely used in clinical practice. However, ICI therapy (monotherapy or combination therapy) is always accompanied by a unique toxicity profile known as immune-related adverse events (irAEs) affecting multiple organs. The endocrine glands are common targets of irAEs induced by ICIs, which cause type 1 diabetes mellitus (T1DM) when the pancreas is affected. Although the incidence rate of ICI-induced T1DM is rare, it will always lead to an irreversible impairment of β-cells and be potentially life-threatening. Hence, it is vital for endocrinologists and oncologists to obtain a comprehensive understanding of ICI-induced T1DM and its management. In our present manuscript, we have reviewed the epidemiology, pathology and mechanism, diagnosis, management, and treatments of ICI-induced T1DM.
Topics: Humans; Immune Checkpoint Inhibitors; Diabetes Mellitus, Type 1; Antineoplastic Agents, Immunological; Antineoplastic Agents; Neoplasms
PubMed: 37390646
DOI: 10.1016/j.intimp.2023.110414 -
Biomedicine & Pharmacotherapy =... Aug 2023The escalating rate of cancer cases, together with treatment deficiencies and long-term side effects of currently used cancer drugs, has made this disease a global... (Review)
Review
The escalating rate of cancer cases, together with treatment deficiencies and long-term side effects of currently used cancer drugs, has made this disease a global burden of the 21st century. The number of breast and lung cancer patients has sharply increased worldwide in the last few years. Presently, surgical treatment, radiotherapy, chemotherapy, and immunotherapy strategies are used to cure cancer, which cause severe side effects, toxicities, and drug resistance. In recent years, anti-cancer peptides have become an eminent therapeutic strategy for cancer treatment due to their high specificity and fewer side effects and toxicity. This review presents an updated overview of different anti-cancer peptides, their mechanisms of action and current production strategies employed for their manufacture. In addition, approved and under clinical trials anti-cancer peptides and their applications have been discussed. This review provides updated information on therapeutic anti-cancer peptides that hold great promise for cancer treatment in the near future.
Topics: Humans; Antineoplastic Agents; Lung Neoplasms; Peptides
PubMed: 37311281
DOI: 10.1016/j.biopha.2023.114996 -
Journal of Nanobiotechnology May 2024Hepatocellular carcinoma (HCC) represents one of the deadliest cancers globally, making the search for more effective diagnostic and therapeutic approaches particularly... (Review)
Review
Hepatocellular carcinoma (HCC) represents one of the deadliest cancers globally, making the search for more effective diagnostic and therapeutic approaches particularly crucial. Aptamer-functionalized nanomaterials (AFNs), an innovative nanotechnology, have paved new pathways for the targeted diagnosis and treatment of HCC. Initially, we outline the epidemiological background of HCC and the current therapeutic challenges. Subsequently, we explore in detail how AFNs enhance diagnostic and therapeutic efficiency and reduce side effects through the specific targeting of HCC cells and the optimization of drug delivery. Furthermore, we address the challenges faced by AFNs in clinical applications and future research directions, with a particular focus on enhancing their biocompatibility and assessing long-term effects. In summary, AFNs represent an avant-garde therapeutic approach, opening new avenues and possibilities for the diagnosis and treatment of HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Humans; Aptamers, Nucleotide; Nanostructures; Animals; Drug Delivery Systems; Antineoplastic Agents
PubMed: 38735927
DOI: 10.1186/s12951-024-02486-5 -
Biomedicine & Pharmacotherapy =... Jan 2024α-Hederin is a monosaccharide pentacyclic triterpene saponin compound derived from the Chinese herb, Pulsatilla. It has garnered considerable attention for its... (Review)
Review
α-Hederin is a monosaccharide pentacyclic triterpene saponin compound derived from the Chinese herb, Pulsatilla. It has garnered considerable attention for its anti-tumor, anti-inflammatory, and spasmolytic pharmacological activities. Given the rising incidence of cancer and the pronounced adverse reactions associated with chemotherapy drugs-which profoundly impact the quality of life for cancer patients-there is an immediate need for safe and effective antitumor agents. Traditional drugs and their anticancer effects have become a focal point of research in recent years. Studies indicate that α-Hederin can hinder tumor cell proliferation and impede the advancement of various cancers, including breast, lung, colorectal, and liver cancers. The principal mechanism behind its anti-tumor activity involves inhibiting tumor cell proliferation, facilitating tumor cell apoptosis, and arresting the cell cycle process. Current evidence suggests that α-Hederin can exert its anti-tumor properties through diverse mechanisms, positioning it as a promising agent in anti-tumor therapy. However, a comprehensive literature search revealed a gap in the comprehensive understanding of α-Hederin. This paper aims to review the available literature on the anti-tumor mechanisms of α-Hederin, hoping to provide valuable insights for the clinical treatment of malignant tumors and the innovation of novel anti-tumor medications.
Topics: Humans; Cell Line, Tumor; Quality of Life; Saponins; Antineoplastic Agents; Liver Neoplasms; Oleanolic Acid
PubMed: 38160624
DOI: 10.1016/j.biopha.2023.116097 -
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 -
Pharmacological Research Apr 2024Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the... (Review)
Review
Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.
Topics: Humans; Antineoplastic Agents; Biological Products; Neoplasms; Drug Resistance, Multiple; Drug Resistance, Neoplasm
PubMed: 38342327
DOI: 10.1016/j.phrs.2024.107099