Caspases are an evolutionary conserved family of cysteine-dependent proteases that are involved in many vital cellular processes including apoptosis, proliferation, differentiation and inflammatory response. Dysregulation of caspase-mediated apoptosis and inflammation has been linked to the pathogenesis of various diseases such as inflammatory diseases, neurological disorders, metabolic diseases, and cancer. Multiple caspase inhibitors have been designed and synthesized as a potential therapeutic tool for the treatment of cell death-related pathologies. However, only a few have progressed to clinical trials because of the consistent challenges faced amongst the different types of caspase inhibitors used for the treatment of the various pathologies, namely an inadequate efficacy, poor target specificity, or adverse side effects. Importantly, a large proportion of this failure lies in the lack of understanding various caspase functions. To overcome the current challenges, further studies on understanding caspase function in a disease model is a fundamental requirement to effectively develop their inhibitors as a treatment for the different pathologies. Therefore, the present review focuses on the descriptive properties and characteristics of caspase inhibitors known to date, and their therapeutic application in animal and clinical studies. In addition, a brief discussion on the achievements, and current challenges faced, are presented in support to providing more perspectives for further development of successful therapeutic caspase inhibitors for various diseases.

Among cell death regulators, members of the Bcl-2 family are of interest because they are highly conserved across species and represent promising targets for anticancer therapy. This family and its associated proteins include more than 25 members, with either anti- or proapoptotic functions. Although the overall regulation of apoptosis by Bcl-2 family proteins is now well understood, targeted therapy requires careful consideration of individual members of the family and their crosstalk. One of the most studied representatives of the Bcl-2 family is antiapoptotic Mcl-1. After 25 years of investigations, a large amount of data regarding Mcl-1's regulation and functions has been compiled. In this review, we summarize current knowledge about Mcl-1, focusing on molecular aspects relevant to Mcl-1 -targeted therapies.

Among cell death regulators, members of the Bcl-2 family are of interest because they are highly conserved across species and represent promising targets for anticancer therapy. This family and its associated proteins include more than 25 members, with either anti- or proapoptotic functions. Although the overall regulation of apoptosis by Bcl-2 family proteins is now well understood, targeted therapy requires careful consideration of individual members of the family and their crosstalk. One of the most studied representatives of the Bcl-2 family is antiapoptotic Mcl-1. After 25 years of investigations, a large amount of data regarding Mcl-1's regulation and functions has been compiled. In this review, we summarize current knowledge about Mcl-1, focusing on molecular aspects relevant to Mcl-1 -targeted therapies.

An emerging role of long non-coding RNAs (lncRNAs) in tumor progression has been revealed in the last decade. Through interactions with nucleic acids and proteins, lncRNAs could act as enhancers, scaffolds or decoys for a number of oncoproteins and tumor suppressors. The aberrant lncRNA expression or mutations are often associated with changes in a variety of cellular processes, including proliferation, stress response and cell death. Here, we will focus on the tumor-associated lncRNAs in ovarian cancer according to their contribution to cancer hallmarks, such as intense proliferation, cell death resistance, altered energy metabolism, invasion and metastasis, and immune evasion. Moreover, the potential clinical implications of lncRNAs and their significance for the diagnosis, prognosis and therapy of ovarian cancer will be discussed.

Genomic instability underlies genesis and the development of various types of cancer. During tumorigenesis, cancer initiating cells assume a set of features, which allow them to survive and proliferate. Different mutations and chromosomal alterations promote a selection of the most aggressive cancer clones that worsen the prognosis of the disease. Despite that caspase-2 was described as a protease fulfilling an initiator and an effector function in apoptosis, it has recently been discovered to play an important role in the maintenance of genomic integrity and normal chromosome configuration. This protein is able to stabilize p53 and affect the level of transcription factors, which activates cell response to oxidative stress. Here we focus on the discussion on the mechanism(s) of how caspase-2 regulates genomic stability and decreases tumorigenesis.

Cancer therapy is aimed at the elimination of tumor cells and acts via the cessation of cell proliferation and induction of cell death. Many research publications discussing the mechanisms of anticancer drugs use the terms "cell death" and "apoptosis" interchangeably, given that apoptotic pathways are the most common components of the action of targeted and cytotoxic compounds. However, there is sound evidence suggesting that other mechanisms of drug-induced cell death, such as necroptosis, ferroptosis, autophagy, etc. may significantly contribute to the fate of cancer cells. Molecular cross-talks between apoptotic and nonapoptotic death pathways underlie the successes and the failures of therapeutic interventions. Here we discuss the nuances of the antitumor action of two groups of the widely used anticancer drugs, i.e., platinum salts and taxane derivatives. The available data suggest that intelligent interference with the choice of cell death pathways may open novel opportunities for cancer treatment.

Cancer therapy is aimed at the elimination of tumor cells and acts via the cessation of cell proliferation and induction of cell death. Many research publications discussing the mechanisms of anticancer drugs use the terms "cell death" and "apoptosis" interchangeably, given that apoptotic pathways are the most common components of the action of targeted and cytotoxic compounds. However, there is sound evidence suggesting that other mechanisms of drug-induced cell death, such as necroptosis, ferroptosis, autophagy, etc. may significantly contribute to the fate of cancer cells. Molecular cross-talks between apoptotic and nonapoptotic death pathways underlie the successes and the failures of therapeutic interventions. Here we discuss the nuances of the antitumor action of two groups of the widely used anticancer drugs, i.e., platinum salts and taxane derivatives. The available data suggest that intelligent interference with the choice of cell death pathways may open novel opportunities for cancer treatment.

Caspases are an evolutionary conserved family of cysteine-dependent proteases that are involved in many vital cellular processes including apoptosis, proliferation, differentiation and inflammatory response. Dysregulation of caspase-mediated apoptosis and inflammation has been linked to the pathogenesis of various diseases such as inflammatory diseases, neurological disorders, metabolic diseases, and cancer. Multiple caspase inhibitors have been designed and synthesized as a potential therapeutic tool for the treatment of cell death-related pathologies. However, only a few have progressed to clinical trials because of the consistent challenges faced amongst the different types of caspase inhibitors used for the treatment of the various pathologies, namely an inadequate efficacy, poor target specificity, or adverse side effects. Importantly, a large proportion of this failure lies in the lack of understanding various caspase functions. To overcome the current challenges, further studies on understanding caspase function in a disease model is a fundamental requirement to effectively develop their inhibitors as a treatment for the different pathologies. Therefore, the present review focuses on the descriptive properties and characteristics of caspase inhibitors known to date, and their therapeutic application in animal and clinical studies. In addition, a brief discussion on the achievements, and current challenges faced, are presented in support to providing more perspectives for further development of successful therapeutic caspase inhibitors for various diseases.

The disruption of apoptotic cell death process is closely associated with the etiology of various diseases, including cancer. Permanent viral infections can cause different types of cancers. Oncogenic viruses manipulate both external and internal apoptosis pathways, and inhibit the activity of proapoptotic proteins and signaling pathways, which facilitates carcinogenesis. Ineffective immune surveillance or immune response suppression can induce uncontrolled virus propagation and host cell proliferation. In this review, we discuss current data that provide insights into mechanisms of apoptotic death suppression by viruses and their role in oncogenesis.

The investigation of cell death mechanisms is one of the fastest growing areas of modern biomedicine. A particular interest in this research topic arose in 1972 after publication of an article by Kerr, Wyllie, and Currie, in which apoptosis, one of the types of cell death, was first considered as a basic biological phenomenon regulating tissue homeostasis. Several Russian groups involved in the investigation of the mechanisms of radiation-induced cell death have drawn attention to the similarity between these two mechanisms. Unfortunately, these studies have been for a long time inaccessible to the international scientific community. These introductory remarks attempt to restore the chain of events that have taken place during the past 50 years.