A Nanotheranostic System Combining Lysosomal Cell Death and Nuclear Apoptosis Functions for Synergistic Cancer Therapy and Addressing Drug Resistance

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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Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

Current Medicinal Chemistry ◽

10.2174/0929867325666180719145819 ◽

2020 ◽

Vol 27 (13) ◽

pp. 2118-2132 ◽

Cited By ~ 5

Author(s):

Aysegul Hanikoglu ◽

Hakan Ozben ◽

Ferhat Hanikoglu ◽

Tomris Ozben

Keyword(s):

Oxidative Stress ◽

Drug Resistance ◽

Side Effects ◽

Cancer Therapy ◽

Tumor Cells ◽

Anticancer Drugs ◽

Chemotherapeutic Agents ◽

Oxidation Reactions ◽

Hybrid Compounds ◽

Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

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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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Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives

Cancers ◽

10.3390/cancers13061292 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1292 ◽

Cited By ~ 1

Author(s):

Shirin Hafezi ◽

Mohamed Rahmani

Keyword(s):

Drug Resistance ◽

Cell Death ◽

Targeted Therapies ◽

Single Agent ◽

Therapeutic Agents ◽

Malignant Cells ◽

Future Perspectives ◽

Comprehensive Overview ◽

Antiapoptotic Proteins ◽

Preclinical And Clinical Studies

The major form of cell death in normal as well as malignant cells is apoptosis, which is a programmed process highly regulated by the BCL-2 family of proteins. This includes the antiapoptotic proteins (BCL-2, BCL-XL, MCL-1, BCLW, and BFL-1) and the proapoptotic proteins, which can be divided into two groups: the effectors (BAX, BAK, and BOK) and the BH3-only proteins (BIM, BAD, NOXA, PUMA, BID, BIK, HRK). Notably, the BCL-2 antiapoptotic proteins are often overexpressed in malignant cells. While this offers survival advantages to malignant cells and strengthens their drug resistance capacity, it also offers opportunities for novel targeted therapies that selectively kill such cells. This review provides a comprehensive overview of the extensive preclinical and clinical studies targeting BCL-2 proteins with various BCL-2 proteins inhibitors with emphasis on venetoclax as a single agent, as well as in combination with other therapeutic agents. This review also discusses recent advances, challenges focusing on drug resistance, and future perspectives for effective targeting the Bcl-2 family of proteins in cancer.

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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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