Результаты поиска

Chimeric Antigen Receptor T-Cell Therapy in Metastatic Castrate-Resistant Prostate Cancer.

Prostate cancer is the most commonly diagnosed solid-organ cancer amongst males worldwide. Metastatic castrate-resistant prostate cancer (mCRPC) is a rapidly fatal end-sequelae of prostate cancer. Therapeutic options for men with mCRPC are limited and are not curative in nature. The recent development of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the treatment of treatment-resistant haematological malignancies, and several studies are underway investigating the utility of this technology in the treatment of solid tumours. In this review, we evaluate the current treatme

Совпадение в полном тексте источника
… Currently, approved therapies from the Food and Drug Administration (FDA) include sipuleucel-T, radium-223, poly (ADP-ribose) polymerase (PARP) inhibitors and checkpoint inhibitors. Radiopharmaceutical agents allow for the delivery of targeted radiotherapy to sites of metastases. …

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]).

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outc

Совпадение в полном тексте источника
… Within the nucleus, TTFields induced DSBs ( Figure 3 B), increased poly(ADP-ribose) polymerase (PARP) cleavage, and enhanced reactive oxygen species (ROS) formation, which downregulated cellular repair and activated cellular apoptosis ( Jo et al., 2018b , 2019 ; Lee et al., 2021 ). …

Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, trigg

Совпадение в полном тексте источника
… Effect of Bortezomib on the expression of molecules involved in apoptosis in HNC cell lines To corroborate that Bortezomib treatment induced apoptosis, the expression of Bax, Bcl-2, procaspases 9/8/3, caspases 9/8/3 and cleavage of poly (ADP-ribose)polymerase-1 (PARP-1) was analyzed by Western blotting …

Antibody-Antineoplastic Conjugates in Gynecological Malignancies: Current Status and Future Perspectives.

In the last decade, antibody-drug conjugates (ADCs), normally formed by a humanized antibody and a small drug via a chemical cleavable or non-cleavable linker, have emerged as a potential treatment strategy in cancer disease. They allow to get a selective delivery of the chemotherapeutic agents at the tumor level, and, consequently, to improve the antitumor efficacy and, especially to decrease chemotherapy-related toxicity. Currently, nine antibody-drug conjugate-based formulations have been already approved and more than 80 are under clinical trials for the treatment of several tumors, especi

Совпадение в полном тексте источника
… Several targeted therapies, including (poly-ADP-ribose polymerase) (PARP) inhibitors and bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, have been approved for ovarian cancer therapies in the last decade [ 76 , 77 ], improving the outcome of this disease. …

miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy.

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system's multiple signalling pathways by binding to the

Совпадение в полном тексте источника
… LNA is also a type of AMOs, but in AMOs, ribose sugar is modified by forming a methyl bridge and this specific modification results in thermal stability, higher water solubility and stabile in the metabolic environment characterizing it as an ideal form for delivery [ 189 ]. …

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma.

The proteasome is crucial for the degradation of intracellular proteins and plays an important role in mediating a number of cell survival and progression events by controlling the levels of key regulatory proteins such as cyclins and caspases in both normal and tumor cells. However, compared to normal cells, cancer cells are more dependent on the ubiquitin proteasome pathway (UPP) due to the accumulation of proteins in response to uncontrolled gene transcription, allowing proteasome to become a potent therapeutic target for human cancers such as multiple myeloma (MM). Up to date, three protea

Совпадение в полном тексте источника
… Additionally, inhibition of proteasome activity leads to the activation of JNK which will eventually cause C-Jun phosphorylation and cleavage of polyADP ribose ( 30 ). …

Towards Drug Repurposing in Cancer Cachexia: Potential Targets and Candidates.

As a multifactorial and multiorgan syndrome, cancer cachexia is associated with decreased tolerance to antitumor treatments and increased morbidity and mortality rates. The current approaches for the treatment of this syndrome are not always effective and well established. Drug repurposing or repositioning consists of the investigation of pharmacological components that are already available or in clinical trials for certain diseases and explores if they can be used for new indications. Its advantages comparing to de novo drugs development are the reduced amount of time spent and costs. In thi

Совпадение в полном тексте источника
… Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells. Breast Cancer Res. 2014;16:R67. doi: 10.1186/bcr3682. 67. …

Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loade

Совпадение в полном тексте источника
… conjugate | Acute lymphoblastic leukemia | Pfizer Dabrafenib/Trametinib combination | Tafinlar ® /Mekinist ® | Kinase inhibitor | Anaplastic thyroid cancer | Novartis Acalabrutinib | Calquence ® | Bruton tyrosine kinase inhibitor | Mantle cell lymphoma | AstraZeneca Niraparib | Zejula ® | Poly ADP ribose …

Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update.

Although survival of multiple myeloma patients has at least doubled during recent years, most patients eventually relapse, and treatment at this stage may be particularly complex. At the time of relapse, the use of alternative drugs to those given upfront is current practice. However, many new options are currently available for the treatment of relapsed multiple myeloma, including recently approved drugs, such as the second- and third-generation proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal antibodies daratumumab and elotuzumab and the

Совпадение в полном тексте источника
… In addition to this receptor function, CD38 acts as an ectoenzyme; CD38 is a cyclic ADP ribose hydrolase that regulates intracellular Ca 2+ influx, leading to the activation of several signaling pathways, eventually leading to the efflux of adenosine, which has an immunosuppressive effect on cytotoxic …

Cancer Stem Cells: The Potential Targets of Chinese Medicines and Their Active Compounds.

The pivotal role of cancer stem cells (CSCs) in the initiation and progression of malignancies has been rigorously validated, and the specific methods for identifying and isolating the CSCs from the parental cancer population have also been rapidly developed in recent years. This review aims to provide an overview of recent research progress of Chinese medicines (CMs) and their active compounds in inhibiting tumor progression by targeting CSCs. A great deal of CMs and their active compounds, such as Antrodia camphorate, berberine, resveratrol, and curcumin have been shown to regress CSCs, in t

Совпадение в полном тексте источника
… Berberine has been shown to induce apoptosis in cancer cells via various pathways such as activating the mitochondrial apoptotic pathway, regulating the activation of Bcl-2 family members as well as activating caspases and inducing the cleavage of poly (ADP-ribose) polymerase-1 (PARP-1). …

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

Epigenetics-targeted drugs: current paradigms and future challenges.

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation. These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences, playing essential roles in organismal development and homeostasis. Conversely, disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases. This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifyin

How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

Совпадение в полном тексте источника
… Poly ADP-ribose polymerase (PARP) is an enzyme known for its involvement in responding to environmental stress-induced DNA damage 166 . … Upon activation, PARP1 catalyzes the attachment of ADP-ribose moieties to histone proteins' amino terminal tails, particularly at H2AK13, H2BK30, H3K27, H3K37 and H4K16 ( Fig. 2 ). …

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021).

PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin-proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article "PROTACs:

Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.

Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs

Совпадение в полном тексте источника
… On the other hand, NAD + -consuming enzymes, namely NAD + glycohydrolase (CD38, CD157, and SARM1), the long-lived protein sirtuin deacetylase family (SIRTs), and poly (ADP-ribose) polymerases (PARPs), are involved [ 217 ]. … in tissues, which means that if NAD + is supplemented by NA, a very high dose is needed to achieve it. 5.1.2 NR In 2004, Bieganowski and Brenner found in their study that yeast can synthesize NAD + through the Preiss-Handler pathway using the direct conversion of NR to NMN assisted by nicotinamide ribose …

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

Совпадение в полном тексте источника
… These two compounds block autophagic flux, resulting in the accumulation of autophagy flux markers LC3-II and p62, along with the cleavage of caspase-3, caspase-9 and poly(ADP-ribose) polymerase 1 (PARP-1), which is a hallmark of caspase-dependent apoptosis [ 77 , 78 ]. …

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance Stefani Spranger, Thomas F. Gajewski K4 Intra

Antibody-Drug Conjugates: Pharmacotherapeutic Properties and Future Perspectives.

Background: The clinical landscape for antibody-drug conjugates (ADCs) is currently experiencing an unprecedented expansion, with more than 20 agents approved to date and hundreds presently under clinical evaluation, underscoring their growing impact in precision oncology. By combining the cytotoxic potency of chemotherapy with the selectivity of monoclonal antibodies, ADCs have redefined targeted cancer therapy. Nevertheless, challenges related to toxicity, resistance, and suboptimal drug delivery continue to limit their full clinical potential. Objectives: This review provides a comprehensiv

Совпадение в полном тексте источника
… Epidermal growth factor receptor; FAP-alpha, Fibroblast activation protein alpha; FGFR2b, Fibroblast growth factor receptor 2b; FOLR1, Folate receptor alpha; GPC3, Glypican-3; HER2, Human epidermal growth factor receptor 2; HER3, Human epidermal growth factor receptor 3; MUC16, Mucin-16; PARP, Poly ADP-ribose …

Thirty years from FDA approval of pegylated liposomal doxorubicin (Doxil/Caelyx): an updated analysis and future perspective.

In 2025, it will be 30 years since the initial clinical approval of pegylated liposomal doxorubicin (PLD) by the Food and Drug Administration. PLD predated the field of nanomedicine and became a model nanomedicine setting key pharmacological principles (prolonged circulation, slow drug release and the enhanced permeability and retention (EPR) effect) for clinical application of other nano-drugs in cancer therapy. The impressive reduction of cardiotoxicity conferred by PLD is the most valuable clinical asset. While PLD has gained a strong foothold in relapsed ovarian cancer and metastatic breas

Совпадение в полном тексте источника
… Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. …

The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.

The field of hematology has experienced a substantial evolution with the acknowledgment of epigenetic processes as essential factors in the development of hematological malignancies. This review article examines the influence of epigenetic alterations, namely DNA methylation and histone modifications, on the onset and advancement of conditions such as acute myeloid leukemia and myelodysplastic syndromes. We discuss how these epigenetic modifications lead to the deregulation of gene expression, eventually promoting leukemogenesis. The emergence of epigenetic therapies, such as DNA methyltransfe

Совпадение в полном тексте источника
… Decitabine is a ribose sugar analog of 5-azacytidine that is much more specific and may be less toxic than 5-azacytidine. This compound has specific activity in myeloid malignancies, MDS, and acute and chronic myeloid leukemia [ 73 , 74 ]. …