Parallel Evolution under Chemotherapy Pressure in 29 Breast Cancer Cell Lines Results in Dissimilar Mechanisms of Resistance

Tegze, Bálint; Szállási, Zoltán; Haltrich, Irén; Pénzváltó, Zsófia; Tóth, Zoltán; Láng, István; Győrffy, Balázs

doi:10.1371/journal.pone.0030804

Cited by 47 publications

(38 citation statements)

References 33 publications

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“…17) In addition, a higher IC 50 value than ours has also been reported recently. 18) At around the IC 50 value obtained in our study (10 to 25 nm), thermo treatment was found to significantly enhance PTX-induced suppression of proliferation in MCF-7 cells. The dose of PTX administered clinically is generally calculated using bodysurface area.…”

Section: Discussionsupporting

confidence: 53%

Short-Term Hyperthermia Promotes the Sensitivity of MCF-7 Human Breast Cancer Cells to Paclitaxel

Liu

et al. 2013

Biological & Pharmaceutical Bulletin

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As a physical adjuvant approach in the treatment of solid tumors, regional hyperthermia plays a synergistic role in enhancing the efficacy of simultaneous chemotherapy. Paclitaxel (PTX) is an anti-mitotic taxane drug that is widely used in chemotherapy for the treatment of various human malignancies such as lung, ovarian, breast, and head and neck cancers. Since the possibility that hyperthermia can enhance the antitumor effects of PTX has not yet been investigated, the present study was designed to evaluate the effects of short-term hyperthermia on PTX-induced antitumor activity in the human breast cancer line MCF-7. It was found that short-term hyperthermia promoted PTX-induced suppression of cell proliferation. The IC 50 for PTX was reduced from 18.2±1.0 to 15.0±0.45 nm (p<0.05). The level of PTX-induced cell apoptosis was increased from 8.5±1.2 to 16.4±2.4% ( p<0.05) and from 15.2±1.4 to 34.9±2.8% (p<0.05), at the end of the first and second hyperthermia cycles, respectively; both the activity and expression of caspase-7 were enhanced. In addition, PTX-induced cell cycle arrest in the G2/M phase was further promoted by short-term hyperthermia, from 9.3±0.7 to 12.5±0.9% (p<0.05). In contrast, short-term hyperthermia affected neither tumor cell migration nor invasion in the presence or absence of PTX. The presented data thus suggest that short-term hyperthermia may serve as a feasible approach in the promotion of breast cancer cell sensitivity to PTX.Key words hyperthermia; paclitaxel; apoptosis; caspase-7; breast cancer Epidemiological studies have revealed that breast cancer is not only the most frequently diagnosed cancer, but also the primary cause of cancer death among females, accounting for 23% of the total cancer burden and 14% of cancer deaths.

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Section: Discussionsupporting

confidence: 53%

Short-Term Hyperthermia Promotes the Sensitivity of MCF-7 Human Breast Cancer Cells to Paclitaxel

Liu

et al. 2013

Biological & Pharmaceutical Bulletin

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“…Dysregulation of DNA repair system and its signaling to checkpoints of cell cycle is strongly associated with the predisposition to several cancers and affects responses to DNA-damaging anticancer therapy [11]. Tubulin alpha 1c, TUBA1C , was associated with chemotherapy resistance in breast cancer cell line [48]. EXOC1 from the gene expression model is a component of the exocyst complex and a multiple protein complex including this gene is vital to target exocytic vesicles to specific docking sites on the plasma membrane.…”

Section: Resultsmentioning

confidence: 99%

Predicting censored survival data based on the interactions between meta-dimensional omics data in breast cancer

Kim

Dudek

et al. 2015

Journal of Biomedical Informatics

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Evaluation of survival models to predict cancer patient prognosis is one of the most important areas of emphasis in cancer research. A binary classification approach has difficulty directly predicting survival due to the characteristics of censored observations and the fact that the predictive power depends on the threshold used to set two classes. In contrast, the traditional Cox regression approach has some drawbacks in the sense that it does not allow for the identification of interactions between genomic features, which could have key roles associated with cancer prognosis. In addition, data integration is regarded as one of the important issues in improving the predictive power of survival models since cancer could be caused by multiple alterations through meta-dimensional genomic data including genome, epigenome, transcriptome, and proteome. Here we have proposed a new integrative framework designed to perform these three functions simultaneously: (1) predicting censored survival data; (2) integrating meta-dimensional omics data; (3) identifying interactions within/between meta-dimensional genomic features associated with survival. In order to predict censored survival time, martingale residuals were calculated as a new continuous outcome and a new fitness function used by the grammatical evolution neural network (GENN) based on mean absolute difference of martingale residuals was implemented. To test the utility of the proposed framework, a simulation study was conducted, followed by an analysis of meta-dimensional omics data including copy number, gene expression, DNA methylation, and protein expression data in breast cancer retrieved from The Cancer Genome Atlas (TCGA). On the basis of the results from breast cancer dataset, we were able to identify interactions not only within a single dimension of genomic data but also between meta-dimensional omics data that are associated with survival. Notably, the predictive power of our best meta-dimensional model was 73% which outperformed all of the other models conducted based on a single dimension of genomic data. Breast cancer is an extremely heterogeneous disease and the high levels of genomic diversity within/between breast tumors could affect the risk of therapeutic responses and disease progression. Thus, identifying interactions within/between meta-dimensional omics data associated with survival in breast cancer is expected to deliver direction for improved meta-dimensional prognostic biomarkers and therapeutic targets.

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“…However, somatic mutations in tubulins have been investigated as a cause of taxane resistance (41). Leandro-Garcia and colleagues (29) have investigated the role of tubulin gene polymorphisms in TRSN using lymphocytes from peripheral blood samples from patients exposed to taxanes in various tumor types and found that polymorphisms in certain genes led to a reduction in susceptibility to TRSN.…”

Section: Discussionmentioning

confidence: 99%

Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel

Abraham

Guo

Dorling

et al. 2014

Clinical Cancer Research

102

100

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Purpose: Associations between taxane-related sensory neuropathy (TRSN) and single-nucleotide polymorphisms (SNP) have previously been reported, but few have been replicated in large, independent validation studies. This study evaluates the association between previously investigated SNPs and TRSN, using genotype data from a study of chemotherapy-related toxicity in patients with breast cancer.Experimental Design: We investigated 73 SNPs in 50 genes for their contribution to TRSN risk, using genotype data from 1,303 European patients. TRSN was assessed using National Cancer Institute common toxicity criteria for adverse events classification. Unconditional logistic regression evaluated the association between each SNP and TRSN risk (primary analysis). Cox regression analysis assessed the association between each SNP and cumulative taxane dose causing the first reported moderate/severe TRSN (secondary analysis). The admixture likelihood (AML) test, which considers all SNPs with a prior probability of association with TRSN together, tested the hypothesis that certain SNPs are truly associated.Results: The AML test provided strong evidence for the association of some SNPs with TRSN (P ¼ 0.023). The two most significantly associated SNPs were rs3213619(ABCB1) [OR ¼ 0.47; 95% confidence interval (CI), 0.28-0.79; P ¼ 0.004] and rs9501929(TUBB2A) (OR ¼ 1.80; 95% CI, 1.20-2.72; P ¼ 0.005). A further 9 SNPs were significant at P-value 0.05.Conclusion: This is currently the largest study investigating SNPs associated with TRSN. We found strong evidence that SNPs within genes in taxane pharmacokinetic and pharmacodynamic pathways contribute to TRSN risk. However, a large proportion of the inter-individual variability in TRSN remains unexplained. Further validated results from GWAS will help to identify new pathways, genes, and SNPs involved in TRSN susceptibility. Clin Cancer Res; 20(9); 2466-75. Ó2014 AACR.

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Parallel Evolution under Chemotherapy Pressure in 29 Breast Cancer Cell Lines Results in Dissimilar Mechanisms of Resistance

Cited by 47 publications

References 33 publications

Short-Term Hyperthermia Promotes the Sensitivity of MCF-7 Human Breast Cancer Cells to Paclitaxel

Short-Term Hyperthermia Promotes the Sensitivity of MCF-7 Human Breast Cancer Cells to Paclitaxel

Predicting censored survival data based on the interactions between meta-dimensional omics data in breast cancer

Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel

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