Abstract
Chemotherapeutic targeting of microtubules has been the standard of care in treating a variety of malignancies for decades. During mitosis, increased microtubule dynamics are necessary for mitotic spindle formation and successful chromosomal segregation. Microtubule targeting agents (MTAs) disrupt the dynamics necessary for successful spindle assembly and trigger programmed cell death (apoptosis). As the critical regulators of apoptosis, anti-apoptotic BCL2 family members are often amplified during carcinogenesis that can result in MTA resistance. This review outlines how BCL2 family regulation is positioned within the context of MTA treatment and explores the potential of combination therapy of MTAs with emerging BCL2 family inhibitors.
Highlights
Chemotherapeutics aim to exploit unique metabolic differences between cancer and normal cells in an effort to kill cancer cells more rapidly than the surrounding healthy tissue
Microtubule targeting agents (MTAs) are often termed “anti-mitotic” due to their significant effect during mitosis, even though microtubule dynamics are involved in processes throughout the cell cycle [3]
Cellular treatment with MTAs disrupts necessary microtubule dynamics during mitosis which results in an increase in spindle assembly checkpoint (SAC) inhibition of the anaphase promoting complex (APC) and SAC dependent mitotic arrest [15]
Summary
Chemotherapeutics aim to exploit unique metabolic differences between cancer and normal cells in an effort to kill cancer cells more rapidly than the surrounding healthy tissue. For this reason, microtubule targeting agents (MTAs, called microtubule poisons) have been employed in treating a variety of malignancies, including hematologic and solid tumors for decades [1]. MTAs are effective, as they target the persistent growth phenotype exhibited by cancer This heightened growth potential is one of the key differences between malignant and healthy cells that allows MTAs to be a standard of care in the treatment of multiple human cancers. The purpose of this review is to outline how BCL2 family regulation is positioned within the context of MTA treatment and the potential that the application of combining MTAs with emerging BCL2 family inhibitors has on improving anti-cancer therapy
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