Review Article

Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

Table 1

Microtubule-destabilizing agents.

Chemical leadProperties and effectsClinical trial/statusReferences

CryptophycinsApoptosis induction. Synergistic with chemotherapy and radiation.Phase II clinical trials in platinum-resistant ovarian cancer and in NSCLC (C-52) but withdrawn due to peripheral neuropathy.[26, 28, 31, 32, 36]

Combretastatin A-4-PAntivascular and antiangiogenic activity. Synergistic with radiation, hyperthermia, chemotherapy, and immunoradiotherapy.Phases II and III clinical trials in advanced solid tumors (lung and thyroid cancer) and in combination with carboplatin.[63, 64, 66ā€“70, 72, 73]

Combretastatin A-1-PAntivascular and antitumoral activity superior to CA-4-P. Synergistic with chemotherapy.Phase I clinical trials in solid tumors and in acute myelogenous leukaemia and myelodysplastic syndromes.[78, 79]

OmbrabulinAntivascular and antitumoral activity superior to CA-4-P. Synergistic with chemotherapy.Phase I clinical trials as a single agent or in combination; phase III clinical trial in advanced soft-tissue sarcoma.[86]

SoblidotinApoptosis induction. Antivascular activity. Antitumoral activity in tumors resistant to vincristine, docetaxel, and paclitaxel.Phase II clinical trials in advanced solid tumors (soft-tissue sarcoma, NSCLC).[99ā€“105]

D-24851Curative at nontoxic doses in rat tumor. No neurotoxic effects. Oral applicability. Activity versus MDR cell lines.Phase I/II clinical trials in advanced solid tumors.[140, 141]

Pseudolaric acid BAntiangiogenic activity. No neurotoxic effects in tested animal. Activity versus MDR cell lines.Preclinical phase.[148, 149]

EmbellistatinAntiangiogenic activity.Preclinical phase.[150]