M-phase specific agents (microtubules)

What are examples of M-phase specific antineoplastic agents?

Vinca alkaloids, taxanes, ixabepilone, eribulin

What is the MOA of m-phase antineoplastic agents?

Target microtubules resulting in mitotic arrest

What are microtubules?

Hollow tubes composed of heterodimer of an a and B tubular. Have a (+) end GTP bound and (-) end.

Which part of microtubules do m-phase antineoplastic agents bind?

(+) end of B-tubulin

Why is Abraxane (2nd gen paclitaxel) better tolerated than Taxol (1st gen)? Higher max tolerated dose.

Smaller size (nanoparticle) and uses human serum albumin instead of cremophor castor oil.

What are outcomes of Abraxane (Nab-paclitaxel)?

Reduced Crephor excipient, enhanced receptor-mediated transcytosis, improved drug accumulation in tumor, reduced off-target toxicity, increase in max tolerated dose

What are mechanisms of resistance towards antimicrotubules?

Up-regulation of B-tubulin expression, mutation of B-tubulin binding sites, efflux pump over expression

How do Eribulin & Vinblastine (Vinca alkaloid) work?

Prevent polymerization of tubulin to microtubule

How do Paclitaxel (Taxanes) and Ixabepilone work?

Prevent collapse of microtubules