Enhanced dermatologic toxicity following concurrent treatment with palbociclib and radiation therapy: A case report

Messer, Jay A.; Ekinci, Ekim; Patel, Tejal; Teh, Bin S.

doi:10.1016/j.rpor.2019.03.001

Cited by 39 publications

(34 citation statements)

References 21 publications

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“…Kettner et al found that targeting interleukin 6 (IL6)/signal transducer and activator of transcription 3 (STAT3) and DNA repair deficiency using a combination STAT3 and poly(ADP-ribose) polymerase (PARP) inhibitor could effectively treat palbociclib-resistant ER+ BC [173]. Messer et al reported a case of the combined use of palbociclib and radiotherapy to enhance the effect of radiotherapy, with improved survival and reduced cell proliferation by G1 cell-cycle arrest [174]. In MDA-MB-231 cells, PTC-209 and palbociclib exhibited more profound dose-dependent cytotoxic effects, leading to inhibition of insulin signaling, focal adhesion, DNA damage response, and Wnt/pluripotency signaling, thereby reducing colony and sphere formation, cell migration, and cell viability [175].…”

Section: The Combined Treatment With Cdk Inhibitors and Other Agentsmentioning

confidence: 99%

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

Ding

Cao

Lin

et al. 2020

IJMS

383

216

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Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose catalytic activities are regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs are key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints and transcriptional events in response to extracellular and intracellular signals. Not surprisingly, the dysregulation of CDKs is a hallmark of cancers, and inhibition of specific members is considered an attractive target in cancer therapy. In breast cancer (BC), dual CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, combined with other agents, were approved by the Food and Drug Administration (FDA) recently for the treatment of hormone receptor positive (HR+) advanced or metastatic breast cancer (A/MBC), as well as other sub-types of breast cancer. Furthermore, ongoing studies identified more selective CDK inhibitors as promising clinical targets. In this review, we focus on the roles of CDKs in driving cell-cycle progression, cell-cycle checkpoints, and transcriptional regulation, a highlight of dysregulated CDK activation in BC. We also discuss the most relevant CDK inhibitors currently in clinical BC trials, with special emphasis on CDK4/6 inhibitors used for the treatment of estrogen receptor-positive (ER+)/human epidermal growth factor 2-negative (HER2−) M/ABC patients, as well as more emerging precise therapeutic strategies, such as combination therapies and microRNA (miRNA) therapy.

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Section: The Combined Treatment With Cdk Inhibitors and Other Agentsmentioning

confidence: 99%

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

Ding

Cao

Lin

et al. 2020

IJMS

383

216

View full text Add to dashboard Cite

show abstract

“…Given these results, the combined treatment seems well-tolerated, whereas severe adverse effects may be a concern. A breast cancer patient with supraclavicular lymph node metastasis was reported to develop grade 3 radiation esophagitis and dermatitis after receiving palbociclib with 40 Gy in 20 fractions to the left neck [ 87 ]. Another case was a breast cancer patient with bone metastases at the left iliac bone and first sacral vertebrae.…”

Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 99%

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

Yang

Luo

Chen

et al. 2020

J Exp Clin Cancer Res

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Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies. Multiple preclinical studies have indicated that CDK4/6 inhibitors exhibit a synergistic effect with radiotherapy both in vitro and in vivo. The principal mechanisms of radiosensitization effects include inhibition of DNA damage repair, enhancement of apoptosis, and blockade of cell cycle progression, which provide the rationale for clinical use. CDK4/6 inhibitors also induce cellular senescence and promote anti-tumor immunity, which might represent potential mechanisms for radiosensitization. Several small sample clinical studies have preliminarily indicated that the combination of CDK4/6 inhibitors and radiotherapy exhibited well-tolerated toxicity and promising efficacy. However, most clinical trials in combined therapy remain in the recruitment stage. Further work is required to seek optimal radiotherapy-drug combinations. In this review, we describe the effects and underlying mechanisms of CDK4/6 inhibitors as a radiosensitizer and discuss previous clinical studies to evaluate the prospects and challenges of this combination.

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“…Twenty-eight patients received concurrent palbociclib and radiotherapy combination only. Two clinical cases presented with grade 3 colitis, grade 2 dermatitis and grade 3 dysphagia [35,40].…”

Section: Palbociclibmentioning

confidence: 99%

CDK 4/6 inhibitors combined with radiotherapy: A review of literature

Bosacki

Bouleftour

Sotton

et al. 2021

Clinical and Translational Radiation Oncology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Enhanced dermatologic toxicity following concurrent treatment with palbociclib and radiation therapy: A case report

Cited by 39 publications

References 21 publications

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

CDK 4/6 inhibitors combined with radiotherapy: A review of literature

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