Autophagic and Apoptotic Effects of HDAC Inhibitors on Cancer Cells

Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and the promotion of tumorigenesis in cancers, novel compounds endowed with histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. Indeed, the potential of HDAC inhibitors for cancer therapy has been explored in preclinical models, and some agents approved for hematologic malignancies have reached the clinical setting. HDAC inhibitors are able to mediate the induction of both apoptosis and autophagy, which are related to anticancer activity in a variety of cancer cell lines. Given the inherent resistance to apoptosis that characterizes cancer, the targeting of alternative pathways is an attractive strategy to improve anti-tumor therapy. The activation of autophagy represents novel cancer treatment targets. This paper aims to critically discuss how the anticancer potential of HDAC inhibitors may elicit a response to human cancers through different cell pathways leading to cell death.

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Regulation of cell death mechanisms by melatonin: implications to cancer therapy

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621999211108090712 ◽

2021 ◽

Vol 21 ◽

Author(s):

Zicheng Wang ◽

Yanqing Liu ◽

Ahmed Eleojo Musa

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Tumor Suppressor ◽

Cancer Cells ◽

Tumor Suppressor Genes ◽

Mammalian Target Of Rapamycin ◽

Therapeutic Modality ◽

Mitotic Catastrophe ◽

Suppressor Genes ◽

Tensin Homolog

: Cancer therapy is based on the killing of cancer cells using various therapeutic agents such as radiation, chemotherapy or targeted therapy drugs and immunotherapy. Cancer cells may undergo apoptosis, mitotic catastrophe, necrosis, autophagy, mitophagy, senescence etc., depending on the therapeutic modality and nature of cancer cells. Mutations in some critical genes such as p53 and phosphatase and tensin homolog (PTEN) tumor suppressor genes are associated with immune escaping cancer cells and progression towards tumor progression. Furthermore, the overexpression of some genes such as phosphatidylinositol-3-kinase (PI3K), nuclear factor of Kappa B (NF-κB), cyclooxygenase-2 (COX-2) and mammalian target of rapamycin (mTOR) is associated with resistance of cancer cells to various types of cell death. Melatonin is known as a circadian regulator hormone that has several anti-cancer properties. It has ability to activate tumor suppressor genes and attenuate the expression of survival genes in cancer cells. Modulation of cell death or survival genes that have been disrupted or overexpressed in cancer cells can improve cancer therapy. In this review, we explain the potentials of melatonin in regulating various mechanisms of cancer cell death.

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New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

Current Medicinal Chemistry ◽

10.2174/0929867324666170830094922 ◽

2018 ◽

Vol 25 (36) ◽

pp. 4758-4784 ◽

Cited By ~ 8

Author(s):

Amy L. Wilson ◽

Magdalena Plebanski ◽

Andrew N. Stephens

Keyword(s):

Clinical Trials ◽

Cell Death ◽

Immune System ◽

Cancer Therapy ◽

Immune Cell ◽

Cytotoxic T Lymphocyte ◽

Tumour Microenvironment ◽

Immune Checkpoints ◽

Tumour Regression ◽

Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

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Lipid-based Nanoplatforms in Cancer Therapy: Recent Advances and Applications

Current Cancer Drug Targets ◽

10.2174/1568009620666200115160805 ◽

2020 ◽

Vol 20 (4) ◽

pp. 271-287 ◽

Cited By ~ 2

Author(s):

Kuldeep Rajpoot

Keyword(s):

Drug Delivery ◽

Cancer Therapy ◽

Adverse Effects ◽

Targeted Drug Delivery ◽

Tumor Therapy ◽

Cancer Therapies ◽

Medication Delivery ◽

Lipid Nanocarriers ◽

Targeted Drug ◽

Drug Nanocarriers

Though modern available cancer therapies are effective, they possess major adverse effects, causing non-compliance to patients. Furthermore, the majority of the polymeric-based medication platforms are certainly not universally acceptable, due to their several restrictions. With this juxtaposition, lipid-based medication delivery systems have appeared as promising drug nanocarriers to replace the majority of the polymer-based products because they are in a position to reverse polymer as well as, drug-associated restrictions. Furthermore, the amalgamation of the basic principle of nanotechnology in designing lipid nanocarriers, which are the latest form of lipid carriers, has tremendous chemotherapeutic possibilities as tumor-targeted drug-delivery pertaining to tumor therapy. Apart from this, it is reported that nearly 40% of the modern medication entities are lipophilic. Moreover, research continues to be efficient in attaining a significant understanding of the absorption and bioavailability of the developed lipids systems.

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Caspase-Independent Pathways of Programmed Cell Death: The Unraveling of New Targets of Cancer Therapy?

Current Cancer Drug Targets ◽

10.2174/156800909789271512 ◽

2009 ◽

Vol 9 (6) ◽

pp. 717-728 ◽

Cited By ~ 55

Author(s):

C. Constantinou ◽

K. Papas ◽

A. Constantinou

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Programmed Cell Death ◽

New Targets

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Hyaluronan based Multifunctional Nano-carriers for Combination Cancer Therapy

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200922113846 ◽

2020 ◽

Vol 20 ◽

Author(s):

Menghan Gao ◽

Hong Deng ◽

Weiqi Zhang

Keyword(s):

Cancer Therapy ◽

Combination Therapy ◽

Cancer Cells ◽

Drug Loading ◽

Tumor Therapy ◽

Drug Carriers ◽

Functional Sites ◽

Therapeutic Modalities ◽

Combination Cancer Therapy ◽

Targeting Strategy

: Hyaluronan (HA) is a natural linear polysaccharide that has excellent hydrophilicity, biocompatibility, biodegradability, and low immunogenicity, making it one of the most attractive biopolymers used for biomedical researches and applications. Due to the multiple functional sites on HA and its intrinsic affinity for CD44, a receptor highly expressed on various cancer cells, HA has been widely engineered to construct different drug-loading nanoparticles (NPs) for CD44- targeted anti-tumor therapy. When a cocktail of drugs is co-loaded in HA NP, a multifunctional nano-carriers could be obtained, which features as a highly effective and self-targeting strategy to combat the cancers with CD44 overexpression. The HA-based multidrug nano-carriers can be a combination of different drugs, various therapeutic modalities, or the integration of therapy and diagnostics (theranostics). Up to now, there are many types of HA-based multidrug nano-carriers constructed by different formulation strategies including drug co-conjugates, micelles, nano-gels and hybrid NP of HA and so on. This multidrug nano-carrier takes the full advantages of HA as NP matrix, drug carriers and targeting ligand, representing a simplified and biocompatible platform to realize the targeted and synergistic combination therapy against the cancers. In this review, recent progresses about HA-based multidrug nano-carriers for combination cancer therapy are summarized and its potential challenges for translational applications have been discussed.

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Magneto Mitochondrial Dysfunction Mediated Cancer Cell Death Using Intracellular Magnetic Nano-Transducers

Biomaterials Science ◽

10.1039/d1bm00419k ◽

2021 ◽

Author(s):

Wooram Park ◽

Seok-Jo Kim ◽

Paul Cheresh ◽

Jeanho Yun ◽

Byeongdu Lee ◽

...

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Mitochondrial Dysfunction ◽

Cancer Cells ◽

Cancer Cell ◽

High Sensitivity ◽

Intrinsic Pathway ◽

Cancer Cell Death

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein,...

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Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?

Clinical Medicine Insights Oncology ◽

10.1177/1179554920976366 ◽

2020 ◽

Vol 14 ◽

pp. 117955492097636

Author(s):

Ah-Reum Jeong ◽

Edward D Ball ◽

Aaron Michael Goodman

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

B Cell ◽

Solid Tumors ◽

Cell Lymphoma ◽

Checkpoint Inhibitors ◽

B Cell Lymphoma ◽

Hematologic Malignancies ◽

Checkpoint Blockade ◽

Programmed Cell Death 1

Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) is 65% to 84% which is the highest among all cancers. Currently, checkpoint inhibitors are only approved for cHL and primary mediastinal B-cell lymphoma as the responses to single-agent checkpoint blockade in other hematologic malignancies is disappointingly low. Various established biomarkers such as programmed cell death 1 ligand 1 (PD-L1) protein surface expression, mismatch repair (MMR) status, and tumor mutational burden (TMB) are routinely used in clinical decision-making in solid tumors. In this review, we will explore these biomarkers in the context of hematologic malignancies. We review characteristic 9p24.1 structural alteration in cHL and primary mediastinal B-cell lymphoma (PMBCL) as a basis for response to PD-1 inhibition, as well as the role of antigen presentation pathways. We also explore the reported frequencies of MMR deficiency in various hematologic malignancies and investigate TMB as a predictive marker.

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