Looking at drug resistance mechanisms for microtubule interacting drugs: does TUBB3 work?
Vinca alkaloids and taxanes represent the mainstay of medical treatment of hematological and solid tumors. Unfortunately, a major clinical problem with these agents is drug resistance. Although a plethora of mechanisms of drug resistance have been described, only a few of them have been validated in clinical trials. Among these, the one involving the protein TUBB3 seems to represent a promising target for studying drug resistance. In fact, it seems that this protein is a factor promoting cell survival and represents an endogenous element of an inherent drug-resistance program built into cells to counteract the activity of microtubule-interacting drugs. Its pivotal role has been ascertained in clinical trials in lung, breast, and ovarian cancer, three diseases that can be successfully treated with microtubule-interacting drugs. Although TUBB3 is probably not a unique factor in drug resistance, the hope is that direct targeting of this protein will increase the response to microtubule-interacting drugs, thereby overcoming an important element in the growth of drug resistance.
Ferlini
Cristiano
C
Laboratory of Antineoplastic Pharmacology, Catholic University of the Sacred Heart, Rome, Italy. cferlini@rm.unicatt.it
Raspaglio
Giuseppina
G
Cicchillitti
Lucia
L
Mozzetti
Simona
S
Prislei
Silvia
S
Bartollino
Silvia
S
Scambia
Giovanni
G
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy*; D017386:Sequence Homology, Amino Acid; D014404:Tubulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C498585:TUBB3 protein, human; D014404:Tubulin