Class III β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel

摘要: Critics have suggested that neoadjuvant chemotherapy (NACT) followed by interval debulking may select for resistant clones or cancer stem cells when compared to primary cytoreduction. β-tubulins are chemotherapeutic targets of taxanes and epothilones. Class III β-tubulin overexpression has been linked chemoresistance hypoxia. Herein, we describe changes in class patients with advanced ovarian carcinoma response NACT, relationship clinical outcome, between who underwent NACT versus debulking; characterize vitro chemosensitivity paclitaxel/patupilone cell lines established from this patient population, expression following repeated exposure paclitaxel. Using immunohistochemistry, observed among 22 paired specimens obtained before/after decreased therapy within stroma (p = 0.07), but not tumor 0.63). Poor median overall survival was predicted high levels both (HR 3.66 [1.11,12.05], p 0.03) 4.53 [1.28,16.1], 0.02). quantitative-real-time-polymerase-chain-reaction higher received (n 12) cytoreduction 14) (mean ± SD fold-change: 491.2 115.9 vs. 224.1 55.66, 0.037). In subculture paclitaxel resulted upregulation, however, overexpressed remained sensitive patupilone. Overexpression dispositioned thus identify an intrinsically aggressive phenotype, predict poor resistance. Decreases stromal represent normalization the microenvironment therapy. Epothilones warrant study carboplatin