Novel Antimicrotubule Agents for Breast Cancer
Abstract
Breast cancer is one of the most frequent malignancies and is the major leading cause of cancer-related deaths in women in the U.S. When local therapies for breast cancer fail and the disease progresses, systemic estrogen ablation therapy, with or without chemotherapy, can lead to tumor regression. However, the disease inevitably progresses to an estrogen-independent state that becomes resistant to hormonal therapy and chemotherapy. In this advanced stage, there are currently no curative therapies as such patients almost always die from their metastatic disease. Thus, there is clearly a pressing need for the development of alternative strategies for this devastating malignancy. Stathmin is the founding member of a family of microtubule destabilizing proteins that regulate the polymerization & depolymerization of the microtubules through its cell cycle specific phosphorylation. Numerous studies, including our own, first demonstrated that stathmin plays an important role in the regulation of cell proliferation. This was followed by the identification of stathmin as a major regulator of the dynamics of microtubules that make up the mitotic spindle. Thus, stathmin is one of the key regulators of the microtubule cytoskeleton and the mitotic spindle. Stathmin promotes microtubule depolymerization either by increasing the rate of microtubule catastrophe or by sequestering tubulin thus depleting the pool of tubulin available for polymerization. Both activities of stathmin are modulated by the interaction of stathmin to two tubulin heterodimers to form a ternary (T2S) stathmin-tubulin complex that directly contributes to the dynamic regulation of microtubules during cell cycle progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2010
- Accession Number
- ADA541469
Entities
People
- Sucharita Mistry
Organizations
- Icahn School of Medicine at Mount Sinai