Resistance to anti-tubulin agents: From vinca alkaloids to epothilones

Krause, W.

doi:10.20517/cdr.2019.06

Cited by 27 publications

(29 citation statements)

References 210 publications

(228 reference statements)

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“…Overall, this mechanism is in contrast to the process observed for taxanes, which function by stabilizing the microtubules after polymer formation and prevent depolymerization (Jordan & Wilson, 2004). (Krause, 2019).…”

Section: Vinca Alkaloidsmentioning

confidence: 71%

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Ultrasound-Microbubble Combined Treatment with Vinca Alkaloids in Prostate Cancer Cells

Gharabeiki¹

2021

Preprint

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Therapeutic efficacy of chemotherapy is highly dependent on the ability to deliver drug molecules across tissue and cellular barriers. Ultrasound stimulated microbubbles (USMB) have been shown to enhance the delivery and cytotoxicity of various classes of chemotherapeutic agents. Here, the application of USMB in combination with the chemotherapeutic class vinca alkaloids is investigated. Specifically, vinorelbine tartrate (VRL) and vinblastine sulfate (VBL) of the vinca alkaloid class, which to the best of our knowledge have not been reported in combination with USMB, were used in this study. Cell viability analysis demonstrated that USMB does not enhance the cytotoxicity of either drug. VRL+USMB showed to have an additive response in cell death, whereas VBL+USMB resulted in an additive effect at a low peak negative pressure, and antagonistic at higher pressures. This work suggests that the mechanism of uptake is an important factor in determining the effectiveness of a chemotherapy drug with USMB treatment.

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Section: Vinca Alkaloidsmentioning

confidence: 71%

“…(b) Binding sites of vinca alkaloids and other microtubule targeting agents. Adapted from(Krause, 2019).…”

mentioning

confidence: 99%

Ultrasound-Microbubble Combined Treatment with Vinca Alkaloids in Prostate Cancer Cells

Gharabeiki¹

2021

Preprint

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“…The latter can be classified as microtubule stabilizers (taxanes and epothilones) that stimulate tubulin polymerization, or destabilizers (vinca alkaloids, colchicine) that inhibit tubulin polymerization [ 141 ]. In rapidly proliferating cancer cells, both events lead to cell cycle arrest and apoptosis [ 142 ]. Mutations in tubulin subunits, changes in the tubulin isotype composition of microtubules, and alterations in microtubule-regulatory proteins are, apart from P-gp engaged in drug efflux [ 7 , 143 ], main factors influencing antitubulin drug resistance [ 141 ].…”

Section: Hybrid Drugs As An Answer To the Anticancer Drug Resistance Problem?mentioning

confidence: 99%

Hybrid Drugs—A Strategy for Overcoming Anticancer Drug Resistance?

2021

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Despite enormous progress in the treatment of many malignancies, the development of cancer resistance is still an important reason for cancer chemotherapy failure. Increasing knowledge of cancers’ molecular complexity and mechanisms of their resistance to anticancer drugs, as well as extensive clinical experience, indicate that an effective fight against cancer requires a multidimensional approach. Multi-target chemotherapy may be achieved using drugs combination, co-delivery of medicines, or designing hybrid drugs. Hybrid drugs simultaneously targeting many points of signaling networks and various structures within a cancer cell have been extensively explored in recent years. The single hybrid agent can modulate multiple targets involved in cancer cell proliferation, possesses a simpler pharmacokinetic profile to reduce the possibility of drug interactions occurrence, and facilitates the process of drug development. Moreover, a single medication is expected to enhance patient compliance due to a less complicated treatment regimen, as well as a diminished number of adverse reactions and toxicity in comparison to a combination of drugs. As a consequence, many efforts have been made to design hybrid molecules of different chemical structures and functions as a means to circumvent drug resistance. The enormous number of studies in this field encouraged us to review the available literature and present selected research results highlighting the possible role of hybrid drugs in overcoming cancer drug resistance.

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“…The frequent exposure to chemotherapy throughout BC treatment—in particular, taxane-based regimens (e.g., paclitaxel, docetaxel) in the adjuvant setting—places evolutionary pressure on tumor cells to acquire genetic and non-genetic properties that evade drug activity ( 5 ). Resistance can be genetically encoded during tumorigenesis, which is typically considered primary resistance, or can be acquired through selection of cancer cells that do not die during the initial phases of treatment, also known as acquired or secondary resistance ( 6 ). Tumor resistance to therapy occurs through the selective upregulation of survival pathways and/or the downregulation of cell death pathways ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Ixabepilone: Overview of Effectiveness, Safety, and Tolerability in Metastatic Breast Cancer

Ibrahim

2021

Front. Oncol.

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Treatment algorithms for metastatic breast cancer describe sequential treatment with chemotherapy and, if appropriate, targeted therapy for as long as the patient receives benefit. The epothilone ixabepilone is a microtubule stabilizer approved as a monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer in patients with demonstrated resistance to anthracyclines and taxanes. While chemotherapy and endocrine therapy form the backbone of treatment for metastatic breast cancer, the epothilone drug class has distinguished itself for efficacy and safety among patients with disease progression during treatment with chemotherapy. In phase III trials, ixabepilone has extended progression-free survival and increased overall response rates, with a manageable toxicity profile. Recent analyses of subpopulations within large pooled datasets have characterized the clinical benefit for progression-free survival and overall survival for ixabepilone in special populations, such as patients with triple-negative breast cancer or those who relapsed within 12 months of prior treatment. Additional investigation settings for ixabepilone therapy discussed here include adjuvant therapy, weekly dosing schedules, and ixabepilone in new combinations of treatment. As with other microtubule stabilizers, ixabepilone treatment can lead to peripheral neuropathy, but evidence-based management strategies may reverse these symptoms. Dose reductions did not appear to have an impact on the efficacy of ixabepilone plus capecitabine. Incorporation of ixabepilone into individualized treatment plans can extend progression-free survival in a patient population that continues to represent an unmet need.

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Resistance to anti-tubulin agents: From vinca alkaloids to epothilones

Abstract: COMMON TRADE NAME(S): vinblastine sulfate injection CLASSIFICATION: mitotic inhibitor 1 Special pediatric considerations are noted when applicable, otherwise adult provisions apply.

Cited by 27 publications

References 210 publications

Ultrasound-Microbubble Combined Treatment with Vinca Alkaloids in Prostate Cancer Cells

Ultrasound-Microbubble Combined Treatment with Vinca Alkaloids in Prostate Cancer Cells

Hybrid Drugs—A Strategy for Overcoming Anticancer Drug Resistance?

Ixabepilone: Overview of Effectiveness, Safety, and Tolerability in Metastatic Breast Cancer

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