TY - JOUR

T1 - Drugs That Changed Society

T2 - Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides

AU - Christensen, Søren Brøgger

PY - 2022

Y1 - 2022

N2 - During a screening performed by the National Cancer Institute in the 1960s, the terpenoid paclitaxel was discovered. Paclitaxel expanded the treatment options for breast, lung, prostate and ovarian cancer. Paclitaxel is only present in minute amounts in the bark of Taxia brevifolia. A sustainable supply was ensured with a culture developed from Taxus chinensis, or with semi-synthesis from other taxanes. Paclitaxel is marketed under the name Taxol. An intermediate from the semi-synthesis docetaxel is also used as a drug and marketed as Taxotere. O-Methylated docetaxel is used for treatment of some paclitaxel-resistant cancer forms as cabazitaxel. The solubility problems of paclitaxel have been overcome by formulation of a nanoparticle albumin-bound paclitaxel (NAB-paclitaxel, Abraxane). The mechanism of action is affinity towards microtubules, which prevents proliferation and consequently the drug would be expected primarily to be active towards cancer cells proliferating faster than benign cells. The activity against slowly growing tumors such as solid tumors suggests that other effects such as oncogenic signaling or cellular trafficking are involved. In addition to terpenoids, recently discovered microtubule-targeting polyketide macrolides and non-ribosomal peptides have been discovered and marketed as drugs. The revolutionary improvements for treatment of cancer diseases targeting microtubules have led to an intensive search for other compounds with the same target. Several polyketide macrolides, terpenoids and non-ribosomal peptides have been investigated and a few marketed.

AB - During a screening performed by the National Cancer Institute in the 1960s, the terpenoid paclitaxel was discovered. Paclitaxel expanded the treatment options for breast, lung, prostate and ovarian cancer. Paclitaxel is only present in minute amounts in the bark of Taxia brevifolia. A sustainable supply was ensured with a culture developed from Taxus chinensis, or with semi-synthesis from other taxanes. Paclitaxel is marketed under the name Taxol. An intermediate from the semi-synthesis docetaxel is also used as a drug and marketed as Taxotere. O-Methylated docetaxel is used for treatment of some paclitaxel-resistant cancer forms as cabazitaxel. The solubility problems of paclitaxel have been overcome by formulation of a nanoparticle albumin-bound paclitaxel (NAB-paclitaxel, Abraxane). The mechanism of action is affinity towards microtubules, which prevents proliferation and consequently the drug would be expected primarily to be active towards cancer cells proliferating faster than benign cells. The activity against slowly growing tumors such as solid tumors suggests that other effects such as oncogenic signaling or cellular trafficking are involved. In addition to terpenoids, recently discovered microtubule-targeting polyketide macrolides and non-ribosomal peptides have been discovered and marketed as drugs. The revolutionary improvements for treatment of cancer diseases targeting microtubules have led to an intensive search for other compounds with the same target. Several polyketide macrolides, terpenoids and non-ribosomal peptides have been investigated and a few marketed.

KW - Faculty of Health and Medical Sciences

KW - Microtubule-targeting agents

KW - Paclitaxel

KW - DOCETAXEL

KW - Cabazitaxel

KW - eribulin

KW - Colchicine

KW - Podophyllotoxin

KW - halochondrin

KW - taccalonolide

KW - zamapanolide

U2 - 10.3390/molecules27175648

DO - 10.3390/molecules27175648

M3 - Review

C2 - 36080414

VL - 27

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 17

M1 - 5648

ER -