Cancer how does it kill
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How Cancer Kills: Mechanisms and Pathways
Cancer, a complex and multifaceted disease, can lead to death through various mechanisms. Understanding these mechanisms is crucial for developing effective treatments and improving patient outcomes. This article explores the primary ways cancer kills, focusing on immune evasion, direct cell killing, and resistance to therapy.
Immune Evasion by Cancer Cells
Cytotoxic Lymphocytes and Immune Surveillance
Cytotoxic lymphocytes (CLs), including cytotoxic T cells (Tc) and natural killer (NK) cells, play a critical role in targeting and killing cancer cells. These immune cells utilize two main pathways: granule exocytosis (involving perforin and granzymes) and death ligands to induce cell death in cancer cells. However, cancer cells can develop mechanisms to evade this immune-mediated killing. For instance, certain genes and pathways enable cancer cells to resist cytotoxic T lymphocyte (CTL)-mediated toxicity, as identified through genome-wide CRISPR screens. These evasion strategies include alterations in the interferon response and tumor necrosis factor (TNF)-induced cytotoxicity pathways.
Tumor Microenvironment and Immune Suppression
The tumor microenvironment (TME) can also contribute to immune evasion. For example, the serine protease inhibitor SerpinB9 (Sb9) can protect tumor cells from granzyme B (GrB)-dependent killing. Inhibiting Sb9 can lead to direct tumor cell death and enhance T cell-mediated immunity, demonstrating a potential therapeutic target.
Direct Cell Killing Mechanisms
Chemotherapy and Radiotherapy
Traditional cancer treatments like chemotherapy and radiotherapy primarily kill cancer cells by inducing DNA damage. These treatments exploit the rapid division of cancer cells, leading to apoptosis or programmed cell death. However, some cancer cells can enter a state of senescence rather than undergoing apoptosis, which can still contribute to the effectiveness of these treatments.
Non-Apoptotic Cell Death Pathways
Recent research has highlighted the importance of non-apoptotic cell death pathways, such as lysosomal-mediated cell death, necroptosis, and autophagy. These pathways provide alternative mechanisms to kill cancer cells, especially those resistant to apoptosis. Understanding and targeting these pathways can offer new therapeutic strategies.
Resistance to Therapy
Mechanisms of Resistance
Cancer cells can develop resistance to cytotoxic agents through various mechanisms. These include alterations in drug transport, metabolism, and the regulation of apoptotic pathways. Additionally, cancer cells may decrease antigen expression or impair the costimulation of T lymphocytes, leading to immune evasion and treatment resistance.
Fractional Killing and Genetic Heterogeneity
The phenomenon of fractional killing, where lethal drugs induce incomplete cell death in a population of cancer cells, further complicates treatment. The kinetics of fractional killing can vary based on the drug, dose, and genetic background of the cancer cells. This variability underscores the need for personalized treatment approaches.
Conclusion
Cancer kills through a combination of immune evasion, direct cell killing, and resistance to therapy. Understanding these mechanisms is essential for developing more effective treatments. By targeting the pathways involved in immune evasion, exploiting non-apoptotic cell death mechanisms, and addressing resistance, we can improve therapeutic outcomes and potentially save more lives.
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