Palbociclib (PD0332991)—a Selective and Potent Cyclin-Dependent Kinase Inhibitor

Clark, Amy S.; Karasic, Thomas B.; DeMichele, Angela; Vaughn, David J.; O’Hara, Mark H.; Perini, Rodolfo F.; Zhang, Paul; Lal, Priti; Feldman, Michael D.; Gallagher, Maryann; O’Dwyer, Peter J.

doi:10.1001/jamaoncol.2015.4701

Cited by 105 publications

(82 citation statements)

References 65 publications

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“…Currently, data on the genetic alterations in these rare tumours are lacking 56 . More specific and patient-targeted therapies are now becoming available for certain noncardiac sarcomas, including agents such as trabectedin (a DNA-damaging agent that specifically targets cells deficient in homologous recombination and immune modulatory properties), palbociclib (a cyclin-dependent kinase 4/6 inhibitor used in the treatment of liposarcomas), pazopanib (a multitargeted tyrosine kinase inhibitor against vascular endothelial growth factors used for nonliposarcomas), and olaratumab (a monoclonal antibody directed against platelet-derived growth factor-α for undifferentiated pleomorphic sarcoma and liposarcoma, in combination with doxorubicin) [57][58][59][60][61][62][63][64][65][66][67] . Whether any of these therapies will have a role in the treatment of cardiac sarcomas is unknown.…”

Section: Hamartoma Of Mature Cardiac Myocytesmentioning

confidence: 99%

Pathology, imaging, and treatment of cardiac tumours

et al. 2017

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Cardiac tumours are a rare, but often devastating, clinical diagnosis. They encompass a broad set of lesions that include both neoplastic and non-neoplastic conditions. Cardiac tumours are often diagnosed incidentally during work-up for other conditions, or during ultrasound, CT, or MRI scans for unusual or nonspecific symptoms. In the past decade, important changes have been made in the nomenclature and the recommendations for diagnosis of cardiac tumours, as highlighted by the WHO's 2015 revision of the classification of cardiac tumours. Moreover, important advances in molecular genetics and therapeutics offer new approaches for the diagnosis and treatment of affected patients. In this Review, we provide an overview of the clinical, pathological, and imaging characteristics of all types of cardiac masses, including both benign and malignant primary cardiac neoplasms.

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Section: Hamartoma Of Mature Cardiac Myocytesmentioning

confidence: 99%

Pathology, imaging, and treatment of cardiac tumours

et al. 2017

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“…Palbociclib inhibits cell growth and DNA replication in a number of retinoblastoma (Rb) proficient human cancer cells, including breast cancer because over 70% of breast cancers are Rb proficient [70]. Palbociclib is a well-tolerated cancer therapeutic [71] that induces G0/G1 arrest in HER2/neu− and HER2/neu+ breast tumor cells [69,72] as well as in neu positive murine mammary tumor cells [73]. Palbociclib can be administered at a concentration of 150 mg/kg through oral gavage and given daily for 3–4 weeks either alone or after the completion of chemotherapy in order to further reduce tumor cell burden.…”

Section: Control Of Cell Cycle Progression Prior To Immunotherapymentioning

confidence: 99%

Conditioning neoadjuvant therapies for improved immunotherapy of cancer

Benson

Manjili

Habibi

et al. 2017

Biochemical Pharmacology

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Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy. To this end, low dose immunogenic chemotherapies, epigenetic modulators and inhibitors of cell cycle progression are potential candidates for rendering tumors highly responsive to immunotherapy. Next generation immunotherapeutics are therefore predicted to be highly effective against cancer, when they are used following appropriate immune modulatory compounds or targeted delivery of tumor cell cycle inhibitors using nanotechnology.

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“…Currently, high specific CDK4/6 inhibitors show a selective and potent therapeutic effect and fewer off-target toxicities than pan-CDK inhibitors for the treatment of breast cancer [14,15]. There are three CDK4/6 inhibitors which deactivate these CDK at <40 nM IC50 values: palbociclib, ribociclib and abemaciclib [16].…”

Section: Palbociclib Is the First Cell Cycle Inhibitor On Demonstratementioning

confidence: 99%

“…The phase 1 trials demonstrated safety, and phase 2 trials have shown single-agent activity with reversible neutropenia as the main toxic effect. The addition of palbociclib to endocrine therapy improves progression-free survival in naive endocrine therapy and resistant metastatic endocrine therapy [15]. The striking clinical activity exhibited by palbociclib in breast cancer announces its additional role in other cancer types.…”

Section: Palbociclib Is the First Cell Cycle Inhibitor On Demonstratementioning

confidence: 99%

Increasing the Potential Targets and Molecularly Targeted Agent Combinations Against Cancer Cell Proliferation

Valdespino¹,

Valdespino-Castillo²,

Valdespino-Castillo³

2017

J Cell Signal

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At least four main groups of intracellular signaling pathways or submodules concur in the cell division and proliferation module: those for the control of the cell cycle, those for the metabolism programming, those for cytoskeleton remodeling, and those for DNA replication and repair. Precise signaling pathways that control cell proliferation module require the joint functional collaboration of signaling pathways of cell growth, cell survival, cell differentiation, intracellular senescence and death programs, and appropriate interaction with angiogenesis, cell micro-environment regulation and immunologic system modules. Seeking out actionable aberrations in cancer cells may now selectively targeted by drug compounds to optimize treatment efficacy and minimize toxicity.This critical review provides an overview of the use of the CDK4/6 inhibitors as the first cell cycle inhibitor that improve the outcomes of patients with HR+ breast cancer. Discusses the connection of different inhibitory agents to modify cell proliferation signaling pathways and sketches the potential use of other molecularly targeted agents in close relationship with proliferation signaling pathways carcinoma cells.

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Palbociclib (PD0332991)—a Selective and Potent Cyclin-Dependent Kinase Inhibitor

Cited by 105 publications

References 65 publications

Pathology, imaging, and treatment of cardiac tumours

Pathology, imaging, and treatment of cardiac tumours

Conditioning neoadjuvant therapies for improved immunotherapy of cancer

Increasing the Potential Targets and Molecularly Targeted Agent Combinations Against Cancer Cell Proliferation

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