Tamoxifen therapy for patients with breast cancer

Neven, Patrick; Joensuu, Heikki; Osborne, Kent; Cardoso, Fátima; Loibl, S.; Linn, Sabine C.; Goldhirsch, A.; Ortmann, O.; Senn, Hans Joerg; Hayes, Daniel F.

doi:10.1016/s0140-6736(13)61237-4

Cited by 2 publications

(1 citation statement)

References 5 publications

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“…Thus, drugs aim to inhibit CDK5 kinase activity may be potential for HCC treatment. TMX, which is the most prescribed hormone therapy for breast cancer, is a new CDK5/p25 interaction blocker and suppresses CDK5 activity eventually [19, 23, 24]. We first confirmed that TMX can disassociate the CDK5-P25 interaction and inhibit CDK5 kinase activity measured by Rb(retinoblastoma) phosphorylation, which is a marker for CDK5 kinase in HCC cells (Fig.…”

Section: Resultsmentioning

confidence: 54%

CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis

Wang

Zhao

Gao

et al. 2019

J Exp Clin Cancer Res

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Background CDK5, an atypical member of the CDK family, play a significant role in the tumorigenesis of multiple organ, but CDK5 and its substrates in genesis and development of HCC is still unclear. Methods Expression of CDK5 in HCC tumor and paired adjacent noncancerous tissues from 90 patients were measured by Western blotting, immunohistochemistry, and real-time PCR. The role of CDK5 in cell function and tumorigenesis was explored in HCC cell lines, ex vivo xenografts and diethylnitrosamine induced HCC model. Furthermore, comparative phosphoproteomic screening identified the oncoprotein TPX2 as a new substrate of CDK5. We also identified the effect of CDK5/P25 interaction blocker tamoxifen on HCC cell growth and migration. Results CDK5 was increased in HCC tisues and the level of CDK5 was correlated with the severity of HCC based on patient recurrence and 5-year fatality rate. Exogenously expressed CDK5 but not kinase-dead CDK5 promoted proliferation, migration, and invasion of HCC cells. Functional ablation of CDK5 significantly inhibited the exacerbation of HCC cells. Xenograft implantation of HCC cells overexpressing CDK5 promoted tumorigenesis, and genetic knockdown of CDK5 reduced HCC growth and metastasis in vivo. More importantly, heterozygous knockout CDK5 (Cdk5+/−) attenuated HCC tumorigenesis induced by diethylnitrosamine. CDK5-mediated phosphorylation of TPX2 at serine 486 promoted its protein stability. TPX2 silence could restore HCC cell migration capability with overexpression CDK5. Treatment with tamoxifen inhibited cell growth and migration of HCC, demonstrating the role of active CDK5 in HCC. Conclusions Our results suggest activation of CDK5 is associated with HCC tumorigenesis. CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular proliferation and tumorigenicity. Electronic supplementary material The online version of this article (10.1186/s13046-019-1297-6) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 54%

CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis

Wang

Zhao

Gao

et al. 2019

J Exp Clin Cancer Res

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The UZ Leuven Policy for Extended Adjuvant Anti-estrogen Therapy in Women With Early Estrogen Receptor-Positive Breast Cancer

Asten

Poppe

Punie

et al. 2015

Curr. Treat. Options in Oncol.

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Opinion statement: Five years after adjuvant endocrine treatment for estrogen receptor (ER)-positive breast cancer, patients have a 2 to 20 % risk of metastatic relapse during the next 5 years. Extended adjuvant endocrine therapy seems to further lower this. In UZ Leuven, extended endocrine therapy is now discussed unless the tumor was a grade 1-2, pT1N0, ER-positive, progesterone receptor (PR)-positive, HER2-negative lesion. After 5 years of adjuvant tamoxifen treatment for ER-positive breast cancer, we encourage women to take another 5 years of tamoxifen. If the tumor was lymph node-positive at diagnosis and patients are menopausal after the first 5 years of tamoxifen, we advise to take prolonged treatment with an oral aromatase inhibitor (AI). For this particular group, available data for extending endocrine therapy with an AI after 5 years of tamoxifen are strongest and more convincing for letrozole than for anastrozole or exemestane. Under these conditions, letrozole is reimbursed for 3 years in Belgium. If women are postmenopausal at diagnosis and already used an oral AI at any time during the first 5 years, we discuss an extra 5 years of tamoxifen. Results from ongoing clinical trials will tell us whether in these cases prolonged AI use is better than tamoxifen so that therapy can be adapted. Benefit from extended adjuvant endocrine therapy is likely larger with better compliance and potential side effects of extended endocrine therapy need to be discussed. Therefore, when advising extended adjuvant endocrine treatment, a balance should always be made between relapse risk and treatment tolerance/compliance.

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Tamoxifen therapy for patients with breast cancer

Cited by 2 publications

References 5 publications

CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis

CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis

The UZ Leuven Policy for Extended Adjuvant Anti-estrogen Therapy in Women With Early Estrogen Receptor-Positive Breast Cancer

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