Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer

Rocca, Andrea; Farolfi, Alberto; Bravaccini, Sara; Schirone, Alessio; Amadori, Dino

doi:10.1517/14656566.2014.870555

Cited by 95 publications

(62 citation statements)

References 83 publications

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“…Aberrations in the cell-cycle pathway have been implicated in human cancer that leads to tumor proliferation, chromosomal instability, and attenuation of genomic integrity (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Cell-Cycle Gene Alterations in 4,864 Tumors Analyzed by Next-Generation Sequencing: Implications for Targeted Therapeutics

Helsten

Kato

Schwaederlé

et al. 2016

Molecular Cancer Therapeutics

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Alterations in the cyclin-dependent kinase (CDK)-retinoblastoma (RB) machinery disrupt cell-cycle regulation and are being targeted in drug development. To understand the cancer types impacted by this pathway, we analyzed frequency of abnormalities in key cell-cycle genes across 4,864 tumors using nextgeneration sequencing (182 or 236 genes; Clinical Laboratory Improvement Amendments laboratory). Aberrations in the cellcycle pathway were identified in 39% of cancers, making this pathway one of the most commonly altered in cancer.

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“…Aberrations in the cell-cycle pathway have been implicated in human cancer that leads to tumor proliferation, chromosomal instability, and attenuation of genomic integrity (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Cell-Cycle Gene Alterations in 4,864 Tumors Analyzed by Next-Generation Sequencing: Implications for Targeted Therapeutics

Helsten

Kato

Schwaederlé

et al. 2016

Molecular Cancer Therapeutics

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“…Pfizer, New York, NY, United States Breast cancer [25] Gastrointestinal tumors [26] P276-00 Cyclin D and CDK-4/6 Piramal Life Sciences Limited, Mumbai, India Mantle Cell Lymphoma [27] Cyclin E and CDK-2 Cyclin A and CDK-2 PHA-848125 Cyclin D and CDK-4/6…”

Section: Resultsmentioning

confidence: 99%

“…Nerviano Medical Sciences, Nerviano, Italy Metastatic solid tumors [27,28] Cyclin E and CDK-2 Cyclin A and CDK-2 LY2835219 Cyclin D and CDK-4/6 Eli Lilly, Indianapolis, IN, United States Lung cancers [29] LEE011 Cyclin D and CDK-4/6 Novartis, Basel, Switzerland Gastrointestinal cancers [30] Breast Cancer [31] AZD5438 Cyclin D and CDK-4/6 Astra Zeneca, London, England Solid malignancies [32] Cyclin E and CDK-2 Cyclin A and CDK-2 Cyclin A and CDK-1 BAY 1000394 Cyclin D and CDK-4/6…”

Section: Resultsmentioning

confidence: 99%

“…Lastly, CDK4 overexpression is linked to a poor prognosis in colorectal cancer [26] . From the list of inhibitors currently in clinical trials, found in Table 1 [23, [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] , there have been a few that have been studied more specifically in colorectal cancer. One that has shown particular promise is PD-0332991, from Pfizer, New York, NY.…”

Section: Cancermentioning

confidence: 99%

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Pharmacological cyclin dependent kinase inhibitors: Implications for colorectal cancer

Balakrishnan

Vyas

Deshpande

et al. 2016

WJG

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Colorectal cancer accounts for a significant proportion of cancer deaths worldwide. The need to develop more chemotherapeutic agents to combat this disease is critical. Cyclin dependent kinases (CDKs), along with its binding partner cyclins, serve to control the growth of cells through the cell cycle. A new class of drugs, termed CDK inhibitors, has been studied in preclinical and now clinical trials. These inhibitors are believed to act as an anti-cancer drug by blocking CDKs to block the uncontrolled cellular proliferation that is hallmark of cancers like colorectal cancer. CDK article provides overview of the emerging drug class of CDK inhibitors and provides a list of ones that are currently in clinical trials.

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“…45 Tumor cell arrest during the G1/S transition, by inhibitors of Cdk4/6, is one of the new avenues for breast carcinoma treatment. 46 While such treatment successfully reduces tumor size, it may also accumulate reactive oxygen species and increase Cyclin D1 expression, 47 which have been linked to increased migration and invasion. 48,49 Hence, understanding of the coordination between cell cycle and cell migration, as well as the other hallmarks of metastasis is increasingly important.…”

Section: Discussionmentioning

confidence: 99%

Directed, but not random, breast cancer cell migration is faster in the G1 phase of the cell cycle in 2D and 3D environments

et al. 2018

Preprint

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Cancer cell migration is essential for the early steps of metastasis, during which cancer cells move through the primary tumor and reach the blood vessels. In vivo, cancer cells are exposed to directional guidance cues, either soluble, such as gradients of growth factors, or insoluble, such as collagen fiber alignment. Depending on the number and strength of such cues, cells will migrate in a random or directed manner. Interestingly, similar cues also stimulate cell proliferation. In this regard, it is not clear whether cell cycle progression affects migration of cancer cells and whether this effect is different in random versus directed migration. In this study, we tested the effect of cell cycle progression on random and directed migration, both in 2D and 3D environments, in the breast carcinoma cell line, FUCCI-MDA-MB-231, using computational image analysis by LEVER. Directed migration in 2D was modeled as chemotaxis along a gradient of soluble EGF inside 10 µm-wide microchannels. In 3D, directed migration was modeled as contact guidance (alignotaxis) along aligned collagen fibers. Time-lapse recordings of cells in 2D and 3D revealed that directed, but not random migration, is cell cycle-dependent. In both 2D and 3D directed migration, cells in the G1 phase of the cell cycle outperformed cells in the G2 phase in terms of migration persistence and instantaneous velocity. These data suggest that in the presence of guidance cues in vivo, breast carcinoma cells in the G1 phase of the cell cycle may be more efficient in reaching vasculature.not peer-reviewed)

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Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer

Cited by 95 publications

References 83 publications

Cell-Cycle Gene Alterations in 4,864 Tumors Analyzed by Next-Generation Sequencing: Implications for Targeted Therapeutics

Cell-Cycle Gene Alterations in 4,864 Tumors Analyzed by Next-Generation Sequencing: Implications for Targeted Therapeutics

Pharmacological cyclin dependent kinase inhibitors: Implications for colorectal cancer

Directed, but not random, breast cancer cell migration is faster in the G1 phase of the cell cycle in 2D and 3D environments

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