Targeting Mitochondria in Cancer Therapy

As mitochondria are gatekeepers of apoptotic signals, targeting mitochondria to induce apoptosis of malignant cells is an important therapeutic strategy. In the past several years, extensive research has focused on screening for chemical compounds, small molecules and peptides that could target the mitochondria. Therapeutic tactics have included strategies that involve the Bcl-2 family proteins, activation of PTPs, the respiratory chain, mitochondrial DNA depletion, and selective targeting of ROS-stressed malignant cells, as well as targeting inhibitors of apoptosis such as IAPs (Dias and Bailly, 2005). Targeting the antiapoptotic members of the Bcl-2 family, namely Bcl-2 and Bcl-XL, and targeting the PTP are among the most studied mechanisms (Dias and Bailly, 2005; O'Neill et al., 2004; Shangary and Johnson, 2003; Walensky, 2006). Targeting of the Bcl-2 family of proteins is discussed in Chapter 8. Here, we will briefly describe strategies for targeting and activation of the PTP.

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