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Caspase-dependent and -independent death pathways in cancer therapy
V M Kolenko1, R G Uzzo, R Bukowski
1Department of Immunology, The Cleveland Clinic Foundation, Ohio 44195, USA. kolenkv@ccf.org
Abstract:
The majority of current anticancer therapies induce tumor cell death through the induction of apoptosis. Alterations in the apoptotic pathways may determine tumor resistance to these therapies. Activation of the proteolytic cascade involving caspase family members is a critical component of the execution of cell death in apoptotic cells. However, recent studies suggest that cell death can proceed in the absence of caspases. In this review we describe the role of caspase-dependent and -independent pathways as targets for anticancer treatment. A better understanding of diverse modes of tumor cell death will help to avoid ineffective treatment and provide a molecular basis for the new strategies targeting caspase-independent death pathways in apoptosis-resistant forms of cancer.
Insights
Most cancer treatments kill tumor cells via apoptosis. This review explores targeting both caspase-dependent and -independent cell death pathways to overcome therapy resistance in apoptosis-resistant cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Current anticancer therapies primarily induce tumor cell death through apoptosis.
- Resistance to these therapies can arise from alterations in apoptotic pathways.
- Caspase activation is crucial for apoptosis, but cell death can occur independently of caspases.
Purpose of the Study:
- To review the roles of caspase-dependent and -independent pathways in cancer.
- To discuss these pathways as potential targets for anticancer treatments.
- To provide a molecular basis for novel strategies against apoptosis-resistant cancers.
Main Methods:
- Literature review of studies on apoptosis and alternative cell death mechanisms.
- Analysis of the molecular components of caspase-dependent and -independent cell death.
- Synthesis of current understanding of resistance mechanisms in cancer therapy.
Main Results:
- Apoptosis, mediated by caspases, is a common mechanism of cancer therapy-induced cell death.
- Tumor resistance to therapy is often linked to dysregulation of apoptotic pathways.
- Caspase-independent cell death pathways represent viable targets for overcoming therapeutic resistance.
Conclusions:
- Understanding diverse tumor cell death modes is crucial for effective cancer treatment.
- Targeting caspase-independent pathways offers a promising strategy for apoptosis-resistant cancers.
- Developing new therapeutic strategies based on diverse cell death mechanisms can improve patient outcomes.