Cytotoxic drugs for patients with breast cancer in the era of targeted treatment: back to the future?

Ribeiro, Joana; Macedo, L. T.; Curigliano, Giuseppe; Fumagalli, Luca; Locatelli, M.; Dalton, Michael; Quintela, A.; Carvalheira, José Barreto Campello; Manunta, Silvia; Mazzarella, Luca; Brollo, Janaína; Goldhirsch, Aron

doi:10.1093/annonc/mdr382

Cited by 46 publications

(43 citation statements)

References 43 publications

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“…[18][19][20][21][22][23] Thus, despite of the toxicity and high resistance rates, taxanes are a mainstay in the clinical landscape. 24 In order to overcome resistance mechanisms and more efficiently kill tumor cells, it was recently proposed to target mitotic exit. [25][26][27][28] Therefore, we decided to compare two opposing strategies to synergize with PTX and potentially circumvent PTX resistance, one that would cause mitotic exit and another that would enhance the mitotic block.…”

Section: Introductionmentioning

confidence: 99%

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

et al. 2013

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Microtubule-poisoning drugs, such as Paclitaxel (or taxol, PtX), are powerful and commonly used anti-neoplastic agents for the treatment of several malignancies. PtX triggers cell death, mainly through a mitotic arrest following the activation of the spindle assembly checkpoint (SAC). Cells treated with PtX slowly slip from this mitotic block and die by mitotic catastrophe. However, cancer cells can acquire or are intrinsically resistant to this drug, posing one of the main obstacles for PtX clinical effectiveness. In order to override PtX resistance and increase its efficacy, we investigated both the enhancement of mitotic slippage and the block of mitotic exit.to test these opposing strategies, we used physiological hyperthermia (Ht) to force exit from PtX-induced mitotic block and the anaphase-promoting complex/cyclosome (APC/C) inhibitor, protAMe, to block mitotic exit. We observed that application of Ht on PtX-treated cells forced mitotic slippage, as shown by the rapid decline of cyclin B levels and by microscopy analysis. Similarly, Ht induced mitotic exit in cells blocked in mitosis by other antimitotic drugs, such as Nocodazole and the Aurora A inhibitor MLN8054, indicating a common effect of Ht on mitotic cells. On the other hand, protAMe prevented mitotic exit of PtX and MLN8054 arrested cells, prolonged mitosis, and induced apoptosis. In addition, we showed that protAMe prevented Ht-mediated mitotic exit, indicating that stress-induced APC/C activation is necessary for Ht-induced mitotic slippage.Finally, Ht significantly increased PtX cytotoxicity, regardless of cancer cells' sensitivity to PtX, and this activity was superior to the combination of PtX with pro-tAMe. Our data suggested that forced mitotic exit of cells arrested in mitosis by anti-mitotic drugs, such as PtX, can be a more successful anticancer strategy than blocking mitotic exit by inactivation of the APC/C.

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Section: Introductionmentioning

confidence: 99%

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

et al. 2013

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“…HAL has been recently developed and is especially promising for the treatment of patients for whom anti-cancer drugs previously failed (5)(6)(7)(8)24). Additional studies focusing on the mechanisms of HAL sensitization and toxicity would be beneficial for future studies examining the utility of HAL as a chemotherapeutic agent in various cancer types.…”

Section: Discussionmentioning

confidence: 99%

Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine

Cheon

Lee

Kim

et al. 2016

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“…Ixabepilone is a semisynthetic analog of the natural product epothilone B, derived from the myxobacterium Sorangium cellulosum [31][32][33] . It is the first agent in its class specifically designed to provide enhanced antitumour activity 34 . Ixabepilone acts by binding to a site on β-tubulin proteins and driving the formation of abnormal mitotic spindles, thereby enhancing microtubule stability [34][35][36] .…”

Section: Ixabepilone: a Novel Epothilone Analogmentioning

confidence: 99%

“…It is the first agent in its class specifically designed to provide enhanced antitumour activity 34 . Ixabepilone acts by binding to a site on β-tubulin proteins and driving the formation of abnormal mitotic spindles, thereby enhancing microtubule stability [34][35][36] . Although the mechanism of action of ixabepilone is similar to that of taxanes, preclinical studies have shown that ixabepilone is structurally different from taxanes and anthracyclines, and binds to tubulin in a distinct manner that makes it less susceptible to mechanisms of drug resistance 32,[36][37][38] .…”

Section: Ixabepilone: a Novel Epothilone Analogmentioning

confidence: 99%

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Advances in the Management of Metastatic Breast Cancer: Options Beyond First-Line Chemotherapy

Ayoub

Verma

2012

Current Oncology

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This article provides an overview of recent advances in chemotherapy that may be used for the treatment of patients with locally advanced or metastatic breast cancer (mbc). Key phase ii and iii trial data for eribulin mesylate, ixabepilone, and nab-paclitaxel, published since 2006, are discussed on the basis of recency, depth, and quality. Eribulin mesylate is the first monotherapy to significantly increase overall survival in patients with pretreated mbc, but nab-paclitaxel offers a novel and safer mode of delivery in comparison with standard taxanes. By contrast, the use of ixabepilone will be limited for now, until the associated neurotoxicity can be better managed. Alongside a brief overview of the other major chemotherapies currently in use, we have aimed to provide a Canadian context for how these novel agents may be integrated into clinical practice.

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Cytotoxic drugs for patients with breast cancer in the era of targeted treatment: back to the future?

Cited by 46 publications

References 43 publications

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine

Advances in the Management of Metastatic Breast Cancer: Options Beyond First-Line Chemotherapy

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