Tumor heterogeneity in ovarian cancer as demonstrated by in vitro chemoresistance assays

Increased paclitaxel resistance in recurrent epithelial ovarian cancer: analysis of metachronous tumors

“…On the other hand, a taxane-free interval longer than 1 year among 34 cases of epithelial ovarian cancer receiving platinum and taxane combination chemotherapy showed significant increased risk of EDR to taxane: paclitaxel 89.7%, and docetaxel 82.8% [2]. Their results were supported by other investigators, and marked increased EDR ratio was seen for paclitaxel [3]. We previously demonstrated increased paclitaxel resistance after postoperative chemotherapy with platinum and taxane in epithelial ovarian, fallopian, and primary peritoneal cancers [4].…”

“…Whether or not ovarian cancer exhibits tumor heterogeneity before and after chemotherapy, demonstrated in an in vitro drug resistance assay, seems to remain controversial [1][2][3][4]. In the largest analysis of an unselected population with ovarian cancer, there was no significant difference in the proportion of extreme drug resistance (EDR) between primary and recurrent cases [1].…”

Predicting platinum resistance in primary advanced ovarian cancer patients with an in vitro resistance index

“…Furthermore, we suggest a mismatch between in vitro resistance and sensitivity in patientmatched primary and metastatic samples (Table 4); however, the number of samples was too small for Wnal conclusions. Previous studies by our group demonstrated 25% variation in DNA ploidy between samples from primary tumor and metastases [20], and tumor heterogeneity has been demonstrated between primary tumor and metastatic samples [21] as well as between primary tumor and samples in recurrent OC [22]. In contrast, Tewari et al [23] found no signiWcant diVerence between in vitro drug resistance in primary and metastatic OC lesions, or primary tumors and recurrent samples.…”

In vitro extreme drug resistance assay to taxanes or platinum compounds for the prediction of clinical outcomes in epithelial ovarian cancer: a prospective cohort study

“…Based on Xow cytometry, tumor heterogeneity has been identiWed in 54% of patients with advanced-stage EOC, suggesting that tumor heterogeneity may play an important role in treatment failure (McAlpine et al 2008). Besides, tumor heterogeneity can lead to diVerences in tumor growth rate, metabolic characteristics, immunogenicity and recovery from exposure to chemotherapeutic agents and it may be a bias in a study for investigating the eYcacy of in vitro EDR assay.…”

“…Nonetheless, the literature on in vitro EDR assay and its utility in guiding treatment of EOC, as well as its impact on survival, are conXicting (McAlpine et al 2008;Albrecht et al 1985). Thus, the current study was prospectively designed to investigate the potential value of in vitro EDR assay to chemotherapeutic agents for the prediction of clinical outcomes in patients with EOC.…”