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CDK4/6 Inhibitor PD0332991 in Glioblastoma Treatment: Does It Have a Future?

Schröder LB, McDonald KL - Front Oncol (2015)

Bottom Line: A specific CDK4/6 inhibitor, PD0332991, obtained accelerated approval from the Food and Drug Administration for the treatment of patients with advanced estrogen receptor-positive and HER2-negative breast cancer.Promising results in in vitro studies, where patient derived glioblastoma cell lines showed sensitivity to PD0332991, gave motive to start in vivo studies.Outcomes of these studies have been contrasting in terms of PD0332991 efficacy within the brain: more research is necessary to conclude whether CDK4/6 inhibitor can be beneficial in the treatment of glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Erasmus Medical Center, Erasmus University Rotterdam , Rotterdam , Netherlands.

ABSTRACT
Glioblastoma is aggressive, highly infiltrating, and the most frequent malignant form of brain cancer. With a median survival time of only 14.6 months, when treated with the standard of care, it is essential to find new therapeutic options. A specific CDK4/6 inhibitor, PD0332991, obtained accelerated approval from the Food and Drug Administration for the treatment of patients with advanced estrogen receptor-positive and HER2-negative breast cancer. Common alterations in the cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway in glioblastoma make PD0332991 also an interesting drug for the treatment of glioblastoma. Promising results in in vitro studies, where patient derived glioblastoma cell lines showed sensitivity to PD0332991, gave motive to start in vivo studies. Outcomes of these studies have been contrasting in terms of PD0332991 efficacy within the brain: more research is necessary to conclude whether CDK4/6 inhibitor can be beneficial in the treatment of glioblastoma.

No MeSH data available.


Related in: MedlinePlus

The cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway. Abbreviations: M – mitosis; G1 – gap 1; S – synthesis; G2 – gap 2; Rb1 – retinoblastoma 1; CDK4/6 – cyclin-dependent kinase 4/6; cycD1 – cyclin D1; P – phosphate group.
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Figure 1: The cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway. Abbreviations: M – mitosis; G1 – gap 1; S – synthesis; G2 – gap 2; Rb1 – retinoblastoma 1; CDK4/6 – cyclin-dependent kinase 4/6; cycD1 – cyclin D1; P – phosphate group.

Mentions: The normal cell cycle consists out of four phases, known as G1, S, G2, and M. Checkpoints regulate progression to the next phase or initiate apoptosis (5). The cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 (cycD1-CDK4/6-Rb1) signaling pathway covers an important checkpoint in the cell cycle (6). It regulates G1 progression to S phase by a cascade of (in)activations (7) (Figure 1).


CDK4/6 Inhibitor PD0332991 in Glioblastoma Treatment: Does It Have a Future?

Schröder LB, McDonald KL - Front Oncol (2015)

The cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway. Abbreviations: M – mitosis; G1 – gap 1; S – synthesis; G2 – gap 2; Rb1 – retinoblastoma 1; CDK4/6 – cyclin-dependent kinase 4/6; cycD1 – cyclin D1; P – phosphate group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663246&req=5

Figure 1: The cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway. Abbreviations: M – mitosis; G1 – gap 1; S – synthesis; G2 – gap 2; Rb1 – retinoblastoma 1; CDK4/6 – cyclin-dependent kinase 4/6; cycD1 – cyclin D1; P – phosphate group.
Mentions: The normal cell cycle consists out of four phases, known as G1, S, G2, and M. Checkpoints regulate progression to the next phase or initiate apoptosis (5). The cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 (cycD1-CDK4/6-Rb1) signaling pathway covers an important checkpoint in the cell cycle (6). It regulates G1 progression to S phase by a cascade of (in)activations (7) (Figure 1).

Bottom Line: A specific CDK4/6 inhibitor, PD0332991, obtained accelerated approval from the Food and Drug Administration for the treatment of patients with advanced estrogen receptor-positive and HER2-negative breast cancer.Promising results in in vitro studies, where patient derived glioblastoma cell lines showed sensitivity to PD0332991, gave motive to start in vivo studies.Outcomes of these studies have been contrasting in terms of PD0332991 efficacy within the brain: more research is necessary to conclude whether CDK4/6 inhibitor can be beneficial in the treatment of glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Erasmus Medical Center, Erasmus University Rotterdam , Rotterdam , Netherlands.

ABSTRACT
Glioblastoma is aggressive, highly infiltrating, and the most frequent malignant form of brain cancer. With a median survival time of only 14.6 months, when treated with the standard of care, it is essential to find new therapeutic options. A specific CDK4/6 inhibitor, PD0332991, obtained accelerated approval from the Food and Drug Administration for the treatment of patients with advanced estrogen receptor-positive and HER2-negative breast cancer. Common alterations in the cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway in glioblastoma make PD0332991 also an interesting drug for the treatment of glioblastoma. Promising results in in vitro studies, where patient derived glioblastoma cell lines showed sensitivity to PD0332991, gave motive to start in vivo studies. Outcomes of these studies have been contrasting in terms of PD0332991 efficacy within the brain: more research is necessary to conclude whether CDK4/6 inhibitor can be beneficial in the treatment of glioblastoma.

No MeSH data available.


Related in: MedlinePlus