Targeting Mitosis in Cancer: Emerging Strategies.
[2024-03-03 16:33:14]
Campbell Family Breast Cancer Institute, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, ON, M5G 2M9, Canada
Campbell Family Breast Cancer Institute, Ontario Cancer Institute, University Health Network, 101 College Street, Toronto, ON, M5G 1L7, Canada
Campbell Family Breast Cancer Institute, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, ON M5G 2M9, Canada. Electronic address: tmak@uhnres.utoronto.ca
The cell cycle is an evolutionarily conserved process necessary for the growth and development of mammalian cells. This process has been a goal of anticancer therapy for decades as cell cycle abnormality is characteristic of cancer. However, despite numerous clinical trials, cell cycle targeted drugs often fail clinically. In this review, we will review briefly the past cell cycle targeted therapies and outline how these drug experiences will help improve and improve antimitotic strategies. An overview of emerging anti-mitotic methods with promising preclinical results is provided and the concept of exploiting the genomic instability of tumor cells by therapeutic inhibition of mitotic checkpoints is discussed. We believe that this strategy is highly likely to succeed, as treatment indices can be increased by targeting tumor-specific vulnerability. This reasoning urged us to develop new inhibitors for key regulators of genomic stability and mitotic checkpoints: AURKA, PLK 4 and Mps 1 / TTK
The relationship between cell cycle and cancer has led to the development of a class of anticancer drugs that specifically target cancer cells during mitosis. According to an article published in the 2012 issue of Cell Death and Disease, "This strategy involves long-term stagnation of cells in mitosis, eventually leading to mitotic cell death." For example, microtubule poisons target microtubules (mitosis). It is the main component of the mitotic spindle) to prevent mitosis. Destroying these thin hollow microscopic protein filaments will eventually prevent sister chromatids from being pulled apart. Examples of microtubule poison are drugs of paclitaxel (paclitaxel) and vinca alkaloids, which are used to treat various cancers, including certain ovarian and breast cancers.
Vinca alkaloids are microtubule targeting agents commonly used in several chemotherapy regimens to perturb cancer cell mitosis. Because these drugs have their own mechanism of action which usually complement the death of cancer cells, they effectively act on several anticancer drug therapies. The most widely used vinca alkaloid is vincristine and most cases with misdirected administration have been reported by improper administration of vincristine 1. The main problem with vincristine is caused by disruption of syringe administration route. Common chemotherapeutic agents for administering vincristine include methotrexate and cytarabine. However, methotrexate and cytarabine were intrathecally administered to maximize their therapeutic effect. Since these drugs are all ready to be administered by syringe, it is already occurring in the sheath to misuse vincristine.
Cancer occurs when cancer tumors arise from uncontrolled single abnormal cells. Primary cancer cells regenerate themselves by a process called mitosis to form two cancer cells. The two cancer cells are divided into 4, then divided into 8, and further divided into 16. Finally, at least 100 million mass of cancer cells are usually required to form a detectable malignancy. The US Environmental Protection Agency has developed a long list of chemical carcinogens. Some of them, including tar, polycyclic aromatic hydrocarbons, phenols, nitrosamines and vinyl chloride are components of tobacco smoke and cause 85% of lung cancer deaths. Other chemical carcinogens may not be known. For example, ethanol in alcoholic beverages is associated with esophageal cancer and aromatic amines in certain dyes can cause bladder cancer.