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The protein that builds the microtubule scaffolding a cell needs to pull its chromosomes apart. Taxanes freeze the scaffold and vinca alkaloids and eribulin stop it forming; either way the dividing cell stalls and dies.
Alpha and beta tubulin dimers assemble into microtubules, the dynamic fibres that form the mitotic spindle, move cargo and shape the cell. Taxanes such as paclitaxel and docetaxel bind beta tubulin and lock microtubules in place; vinca alkaloids such as vincristine and the halichondrin analogue eribulin bind the growing ends and stop assembly. Both leave the spindle unable to segregate chromosomes, triggering mitotic arrest. The same mechanism carries the MMAE payload of brentuximab vedotin and enfortumab vedotin and the maytansinoid payload of trastuzumab emtansine. Peripheral neuropathy, from microtubule damage in long axons, is the shared dose-limiting toxicity.
In plain words · The protein that builds the microtubule scaffolding a cell needs to pull its chromosomes apart. Taxanes freeze the scaffold and vinca alkaloids and eribulin stop it forming; either way the dividing cell stalls and dies.
The protein that builds the microtubule scaffolding a cell needs to pull its chromosomes apart. Taxanes freeze the scaffold and vinca alkaloids and eribulin stop it forming; either way the dividing cell stalls and dies.
Heterodimeric building block of microtubules; drug binding at the taxane, vinca or maytansine site disrupts spindle dynamics.
4 products aim at Tubulin (microtubules): antibody-drug conjugates and other agents. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
Broadly expressed or essential: HPA lists TUBB among essential proteins and finds the RNA at low tissue specificity; the 8 medicines aimed at it (Paclitaxel / nab-paclitaxel, Docetaxel, Vincristine and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA TUBB: RNA low tissue specificity; high antibody staining in 9 normal tissues; highest cancer staining testis cancer (3 of 11 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Lung cancer (all types), Ovarian cancer, Leukaemia); approvals of single-target medicines aimed at it also list Prostate cancer, not counted; Open Targets associates it with 19 specific cancer types at or above 0.5 (breast cancer, non-small cell lung carcinoma, breast carcinoma, Hodgkins lymphoma, plasma cell myeloma, diffuse large B-cell lymphoma and more). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas TUBB tissue; Open Targets ENSG00000196230 associations
First described 1983. Earliest sequence paper UniProt cites for the protein: Lee M.G.-S. et al, Cell, 1983, "Evolutionary history of a multigene family: an expressed human beta-tubulin gene and three processed pseudogenes". Source.
Heterodimeric building block of microtubules; drug binding at the taxane, vinca or maytansine site disrupts spindle dynamics.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Bone marrow, Breast, Cerebral cortex, Colon, Endometrium, Esophagus.
Medium only: breast cancer, cervical cancer, colorectal cancer, endometrial cancer.
HPA TUBB tissue · HPA TUBB pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | Housekeeping enzyme present in every dividing cell (microtubule scaffold for cell division); not a selection marker, which is why these drugs are given by cancer type rather than by test. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Depatuxizumab mafodotin carried a cell-killing payload to glioblastomas with extra copies of the EGFR gene. It caused serious eye problems and, in the phase 3 INTELLANCE-1 trial, did not help patients live longer, so development stopped in 2019.
Estramustine is an oral prostate cancer drug that combines an oestrogen with an alkylating agent, approved in the United States in 1981 for metastatic disease and later combined with taxanes, though its clotting risk has pushed it out of routine use.
Utidelone is Biostar Pharmaceuticals' epothilone chemotherapy, approved in China in 2021 with capecitabine for advanced breast cancer after anthracyclines and taxanes.
Vindesine is a vinca alkaloid, a semi-synthetic relative of vinblastine, used in Europe and elsewhere for acute lymphoblastic leukaemia and some solid tumours; it was never marketed in the United States.
Query for this target: (TITLE:"Tubulin" OR ABSTRACT:"Tubulin" OR TITLE:"microtubules" OR ABSTRACT:"microtubules" OR TITLE:"TUBB" OR ABSTRACT:"TUBB") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Tubulin (microtubules), not a curated reading list.
Shares Estramustine, Docetaxel.
Shares Estramustine, Docetaxel.
Shares Estramustine, Paclitaxel / nab-paclitaxel.
Shares Utidelone, Non-small-cell lung cancer.
Shares Docetaxel, Paclitaxel / nab-paclitaxel, Ovarian cancer, HR-positive / HER2-negative breast cancer.
Shares Vindesine, Vincristine.
Shares Estramustine, Docetaxel.
Shares Eribulin, Paclitaxel / nab-paclitaxel, Ovarian cancer.