Class III β-tubulin expression in tumor cells predicts response and outcome in patients with non–small cell lung cancer receiving paclitaxel

Abstract

Both fundamental and clinical studies suggest that class III B-tubulin expression is associated with resistance to taxanes and constitutes a prognostic factor in several solid tumors. In this study, we assessed the prognostic and predictive value of class III B-tubulin in tumors of patients with locally advanced or metastatic non -small cell lung cancer (NSCLC) treated with paclitaxel-based or other regimens that did not include tubulin-binding agents. Expression of class III B-tubulin was examined immunohistochemically in 91 tumor samples obtained before treatment from patients with stage III and IV NSCLC, including 47 who received paclitaxel-based regimens and 44 who received regimens without tubulin-binding agents. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of class III B-tubulin protein. The response rate was 37.5% (16 responses among 45 evaluable patients) among patients receiving paclitaxel. Patients whose tumors expressed low levels of class III B-tubulin isotype had a better response rate, longer progression-free survival, and overall survival (P < 0.001, 0.004, and 0.002, respectively), whereas this variable was not found to be predictive in patients receiving regimens without tubulinbinding agents. A multivariate analysis taking into account sex, age, histology, stage, and class III B-tubulin confirmed that low-level class III B-tubulin expression was independently correlated with progression-free survival (P = 0.003) and overall survival (P = 0.003). These findings suggest that the expression levels of class III B-tubulin in tumor cells is predictive of response to therapy and patient outcome in patients with NSCLC receiving paclitaxel-based chemotherapy but is not a general prognostic factor in this patient population.

Cytoskeleton and paclitaxel sensitivity in breast cancer: The role of β‐tubulins

“…The only other available study 39 on breast cancer patients treated with neoadjuvant docetaxel reported that Class III b tubulin mRNA increase was associated with a poorer probability of clinical response to docetaxel. Other clinical experiences concerning Class III b tubulin and response to taxanes were conducted in small series of patients with ovarian, 40 epithelial lung advanced cancers 41,42 or gastric cancer 43 confirming a relationship between of Class III b tubulin tumor expression and paclitaxel-resistance. These studies considering Class III b tubulin expression but also other potential biomarkers involved in mechanisms of paclitaxelresistance concluded that this b tubulin isoform could be 1 of the most relevant mechanism for clinical resistance to taxanes.…”

Melanoma cell sensitivity to Docetaxel‐induced apoptosis is determined by class III β‐tubulin levels

“…More recently, acquired expression of class III b-tubulin was not seen in another study of ovarian cancer, however, the pre-treatment level of this isotype did act as an independent prognostic indicator of poor outcome [26]. Similarly, increased expression of classes I and III b-tubulin in breast [27] and class III b-tubulin non-small cell lung cancer [28] also appear to predict poor outcomes with Paclitaxel and Docetaxel, respectively.…”

Roles and Mechanisms of Estrogen and Estrogen Receptors in Breast Cancer Resistant to Chemotherapy

“…stathmin, tau), as well as enhanced 3-tubulin expression might be correlated with reduced response to antimicrotubule agentbased chemotherapy or worse outcome in a variety of tumor settings. In in vitro studies or in clinical investigations, enhanced expression of 3-tubulin has shown to play a crucial role in the development of chemoresistance to antimicrotubule agents in a variety of tumors such as lung, breast, prostate or orarian cancers (61)(62)(63)(64)(65)(66), and has be considered as a predictive marker of paclitaxel resistance (25,(67)(68)(69)(70). Nevertheless, the mechanism underlying 3-tubulin expression still remains unclear.…”