Table 5. A quick summary of all included articles in this review.

Author of the publication	Aim of the study	Year of the study	Type of the study	Main findings
Neophytou et al. [16]	Reveal the major apoptosis pathways and illustrate how pro-apoptotic and anti-apoptotic proteins are modified in malignant cells to produce drug resistance.	2021	Review	Disruption of major apoptosis pathways can cause drug resistance. For example, disruption in B-cell lymphoma 2 (Bcl-2) levels and p53 inactivation have been seen in different types of multiple drug-resistant malignancies.
Mohammad et al. [17]	Provide a full picture of successful anti-cancer techniques that can overcome resistance to apoptosis to produce a better therapeutic outcome in patients with malignancy.	2015	Review	Apoptotic therapy needs a good choice of therapeutic techniques with a wide knowledge of determinants associated with therapy resistance, firstly by sorting the main reasons for apoptosis resistance and providing a list of prioritized targeted therapy.
Carneiro et al. [18]	Describe apoptosis pathways, signaling pathways that affect them, molecular targets, and clinical therapy.	2020	Review	Multiple pathways of inducing apoptosis are required in cancer cells, some more direct than others, mostly through the final common pathway that requires caspase-dependent proteolysis, membrane blebbing, and deoxyribonuclease (DNase)-dependent breakdown of chromosomal deoxyribonucleic acid (DNA).
Xu et al. [19]	Summarize the current understanding and knowledge of apoptosis and apoptotic bodies. Discuss apoptosis-related therapeutic applications.	2019	Review	There are different ways by which apoptosis can show itself, with multiple cells following different breakdown routes, eventually leading to the liberation of apoptotic bodies.
Strasser et al. [20]	Focus on the target of action of drugs that kill malignant cells by directly activating apoptosis machinery and synergizing with chemotherapy and targeted agents to provide better outcomes for cancer patients.	2020	Review	Clinically, the B-cell lymphoma 2 (Bcl-2) specific inhibitor venetoclax has been proven to be an excellent novel target for cancer treatment. Research on venetoclax is continuing with nearly 200 randomized controlled trials (RCTs) planned. These will eventually show the cancers that are more susceptible and the kind of resistance that may appear.
Singh et al. [21]	Provide recent insights into the dynamic relations between the B-cell lymphoma 2 (Bcl-2) proteins and how they control apoptotic cell death in cells to achieve new opportunities for therapeutic interventions.	2019	Review	Strong fundamental knowledge of Bcl-2 family protein function is crucial for choosing therapies, monitoring responses, and understanding mechanisms of drug resistance.
Yuan et al. [22]	Discuss the role of ubiquitination and deubiquitination in apoptosis and apoptotic cell clearance.	2022	Review	Ubiquitination is required for various cell functions and almost all aspects of growth and development. Multiple signaling pathways and genes are involved in ubiquitination.
Deng et al. [15]	Evaluate the relationship between the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and neurological recovery in patients after traumatic brain injury (TBI).	2020	Systemic review	Improved connection between B-cell lymphoma 2 (Bcl-2) and apoptosis can help develop targeted therapies to decrease secondary neuronal loss. In neurons vulnerable to programmed cell death, increasing Bcl-2 levels produce a neuroprotective role and a field for a biomarker with diagnostic capability.
Spanheimer et al. [23]	Study the effect of taking vandetanib before surgery on proliferation and apoptosis markers in breast cancer.	2021	Randomized controlled trial	No statistically significant differences were shown with vandetanib compared to placebo. An unjustified claim was that treating with vandetanib will reduce phosphorylated extracellular signal-regulated kinase (p-ERK) and produce better effects in rearranged during transfection (RET)-expressing tumors.
Zerp et al. [24]	Evaluate combined effects of radiation and B-cell lymphoma 2 (Bcl-2) inhibitor AT-101 in head and neck squamous cell carcinoma (HNSCC).	2015	Randomized controlled trial	B-cell lymphoma 2 (Bcl-2) Inhibitor AT-101 leads to potentiation of radiotherapy-dependent apoptosis in head and neck squamous cell carcinoma in vitro, which further encourages the use of AT-101 in Bcl-2 expressing malignancies.