What drugs target microtubules?
Many new drugs that target microtubules are in clinical trials and large numbers of microtubule-active compounds are being developed. Among the most successful microtubule-targeted chemotherapeutic drugs are paclitaxel and the Vinca alkaloids, which were previously thought to work through opposite mechanisms.
Why would drugs that target microtubules be effective in the treatment of cancer?
The inhibition of microtubule function by MTAs causes inhibition of the AKT/mTOR signaling pathway and thus inhibits cancer cell proliferation. This mechanism is independent of MTAs induced mitotic arrest and could provide an alternative mechanism of drug action that can explain its clinical activity.
Which cytoskeleton is targeted by some anticancer drugs?
Microtubules and actin filaments play important roles in mitosis, cell signaling, and motility. Thus these cytoskeletal filaments are the targets of a growing number of anti-cancer drugs.
Which of the following are used in cancer chemotherapy and act by stabilizing microtubules?
2.4. 3 Gemcitabine–Abraxane. Paclitaxel is a commonly used chemotherapeutic drug most often used in breast, lung, and ovarian cancer, and AIDS-related sarcomas. As a microtubule inhibitor, paclitaxel acts to stabilize polymerized microtubules during mitosis, thus leading to cell cycle arrest in the G2 and M phases.
What drugs stabilize microtubules?
In vitro, the most widely used microtubule-stabilizing agent is the plant-derived compound paclitaxel [13]. It has been used as a chemotherapeutic drug despite its severe disadvantages, such as insolubility in water [14] and high toxicity [15].
Which of the following drug that binds to tubulin and prevents its polymerization?
Vinca dimer indole alkaloids (e.g. vinblastine) act as spindle poisons. They bind tubulin, inhibiting polymerisation into microtubules, the major elements of the cytoskeleton [100]. Vinblastine itself and its analogue vinorelbine (Navelbine®) [101] are marketed for cancer therapies (Fig. 36).
What is the role of tubulin in cancer?
In the context of cancer, the tubulin family of proteins is recognized as the target of the tubulin-binding chemotherapeutics, which suppress the dynamics of the mitotic spindle to cause mitotic arrest and cell death.
Which of the anticancer drugs act at specific sites binds tubulin and inhibit microtubule formation?
Colchicine analogues blocks cell division by disrupting the microtubule. It has been reported that the β-subunit of tubulin is involved in colchicine binding. It binds to the soluble tubulin to form colchicine-tubulin complex.
What is taxol used for in medicine?
Paclitaxel is used to treat various types of cancer. It is a cancer chemotherapy drug that works by slowing or stopping cancer cell growth.
What drugs inhibit microtubules?
Microtubule inhibitors (MTI) such as taxanes, vinca alkaloids, and epothilones stabilize or destabilize microtubules, thereby suppressing microtubule dynamics required for proper mitotic function, effectively blocking cell cycle progression and resulting in apoptosis.
How does colchicine work on microtubules?
Colchicine is a classical anti-mitotic drug which blocks mitotic cells in metaphase. It binds to soluble tubulin to form tubulin-colchicine complexes in a poorly reversible manner, which then binds to the ends of microtubules to prevent the elongation of the microtubule polymer.
Which microtubules as a target for anticancer drugs?
Microtubules as a target for anticancer drugs 1 The Vinca alkaloids. The Vinca alkaloids have been responsible for many chemotherapeutic success… 2 Paclitaxel and related drugs. Paclitaxel and its semi-synthetic analogue docetaxel were among… 3 Colchicine. Colchicine is used clinically in the treatment of gout,…
What are microtubules and why are they important?
Microtubules and their dynamics are the targets of a chemically diverse group of antimitotic drugs (with various tubulin-binding sites) that have been used with great success in the treatment of cancer ( Table 1 ).
What is the pathophysiology of microtubule-targeted drug resistance?
Development of resistance to microtubule-targeted drugs has several possible causes, some of which might involve changes in microtubule dynamics resulting from altered expression of tubulin isotypes, tubulin mutations, and altered expression or binding of microtubule-regulatory proteins. Microtubule-targeted drugs can synergize with one another.
How do microtubule-targeted drugs interact with each other?
Microtubule-targeted drugs can synergize with one another. Understanding their modes of action might lead to improved dosing regimens and combinations with other microtubule-targeted drugs, as well as combinations with ‘molecularly targeted’ drugs.