Changing the expression vector of multidrug resistance genes is related to neoadjuvant chemotherapy response

Litviakov, N. V.; Чердынцева, Н. В.; Цыганов, М. М.; Denisov, Evgeny V.; Garbukov, Evgeny Yu.; Мерзлякова, М К; Волкоморов, В. В.; Vtorushin, S. V.; Zavyalova, М. V.; Slonimskaya, Е. М.; Perelmuter, V. M.

doi:10.1007/s00280-012-1992-x

Cited by 32 publications

(34 citation statements)

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“…The data of our previous study suggest that changes in expression of MDR genes during the chemotherapy process or the development of adaptive MDR, but not the mRNA levels of these genes per se, are associated with NAC efficiency. In particular, reduction in MDR gene expression in post-NAC samples in comparison with pre-NAC tumors was linked with good response to chemotherapy, whereas patients displaying MDR gene upregulation exhibited resistance to therapy15. In addition, recent data indicate that chemotherapy-induced upregulation of MDR genes can result in decreased distant metastasis-16 and disease-free17 survival.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression

Denisov

Litviakov

Zavyalova

et al. 2014

Sci Rep

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In this study, the influence of intratumoral morphological heterogeneity of breast cancer on neoadjuvant chemotherapy (NAC) efficiency was investigated. In particular, we analysed the association of NAC response and pre- and post-NAC expression of the main multidrug resistance (MDR) genes - ABCB1, ABCC1, ABCC5, ABCG1, and ABCG2, with the presence of different morphological structures in breast tumors. In addition, the expression of MDR genes was investigated in different morphological structures and in their microenvironment by comparing probes obtained using laser microdissection. The results of this study showed that tumors with alveolar structures were more frequently NAC-nonresponsive than cases without this structural type (p = 0.0028, Bonferroni-corrected p = 0.014). The presence of trabecular structures in breast tumors was also associated with chemoresistance (p = 0.0272, Bonferroni-corrected p = 0.136). High expression of MDR genes was not found in alveolar structures (including their microenvironment) and in tumors containing this structural type. In contrast, more active MDR genes and expression of the ABCB1 gene were found only in trabecular structures. Taken together, our data indicate that breast tumors with alveolar structures possess resistance to NAC, which is not related to high expression of MDR genes, whereas chemoresistance of tumors with trabecular structures can depend on the expression level of ABCB1.

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Section: Discussionmentioning

confidence: 99%

Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression

Denisov

Litviakov

Zavyalova

et al. 2014

Sci Rep

Self Cite

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“…We have found that the decrease in -transporter expression during the neoadjuvant treatment relates to drug response. In contrast, the increase in the ABC gene expression was associated with no clinical response to treatment [13].…”

Section: Multidrug Resistancementioning

confidence: 65%

“…All patients with deletions of 1 3 ABCC5 gene loci, and most patients having deletions in 1 (16p13.1), 2 (10q24), ABCG1 (21q22.3), ABCG2 (4q22.1), responded favorably to NAC. So, our study demonstrated that deletion MDR gene loci can be used as predictive marker for tumor response to NAC [13,14]. We performed the prospect study to examine whether the detection of new markers for prognosis of tumor response can be useful to choose the optimal therapy.…”

Section: Multidrug Resistancementioning

confidence: 99%

The molecular aspects of personalized anticancer treatment

Чердынцева¹,

Litviakov²,

Ivanova³

et al. 2016

AIP Conference Proceedings

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Abstract. Only 25% of cancer patients, on average, benefit from therapy. Even in the cases of complete clinical response the tumor progression is an event of high level expectation. The main reasons for tumor progression are: intratumor heterogeneity resulted from clonal evolution, drug resistance, and tumor-promoting microenvironment. The reprogramming of microenvironmental stromal-inflammatory components is expected to allow tumor phenotype reversion. So, to find the new effective markers of tumor progression, drug response and targets for therapy, it could be promising to take into account the tumor-microenvironment heterogeneity and tumor clonal evolution.

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“…To date, there have been no studies reporting on changes in b3-tubulin expression during the course of chemotherapy. It has been shown that during the course of chemotherapy, expression changes may occur in some molecules, and these changes are often closely associated with drug resistance [15,16]. The goal of the present study is to explore the role of b3-tubulin expression in resistance to taxane-containing chemotherapy by examining b3-tubulin expression before and throughout the course of chemotherapy.…”

Section: Introductionmentioning

confidence: 98%

β3-tubulin is a good predictor of sensitivity to taxane-based neoadjuvant chemotherapy in primary breast cancer

et al. 2015

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The objective of this study was to explore the relationship between β3-tubulin expression and sensitivity to taxane-based neoadjuvant chemotherapy in primary breast cancer patients. A total of 48 local advanced breast cancer patients that received taxane-containing neoadjuvant chemotherapy were studied. The levels of β3-tubulin expression were tested by immunohistochemistry before chemotherapy and at the end of cycles 2, 4 and 6. The correlation between the efficacy of the chemotherapy and β3-tubulin expression and changes in β3-tubulin expression over the course of chemotherapy was examined. β3-tubulin protein expression before chemotherapy was significantly and negatively correlated with the response rate. The overall response rate was 31.8 % in the high β3-tubulin expression group, whereas it was 84.6 % in the low β3-tubulin expression group. At the end of cycles 2, 4 and 6 during the treatment course, the average expression rates of β3-tubulin were showed an increasing trend with β3-tubulin expression level at the end of cycle 4 being significantly different from that before chemotherapy. Nine patients that had a low β3-tubulin expression level preneoadjuvant chemotherapy changed to a high β3-tubulin expression level postneoadjuvant chemotherapy, and they had lower response rate than patients with consistent low. In conclusion, β3-tubulin is a good predictor of chemosensitivity to taxane for breast cancer, and the change of its expression level during chemotherapy may be an important cause of secondary resistance to taxane. Detection of β3-tubulin expression before and throughout the chemotherapy will help with selection of the chemotherapy treatment plan.

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Changing the expression vector of multidrug resistance genes is related to neoadjuvant chemotherapy response

Abstract: Our results suggest that reductions in MDR gene expression in post-NAC samples in comparison with pre-NAC are associated with tumor response to FAC and CAX as well as taxotere-based NAC, while patients displaying MDR gene upregulation had resistance to therapy.

Cited by 32 publications

References 50 publications

Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression

Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression

The molecular aspects of personalized anticancer treatment

β3-tubulin is a good predictor of sensitivity to taxane-based neoadjuvant chemotherapy in primary breast cancer

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