Efficacy of PHA-848125, a Cyclin-Dependent Kinase Inhibitor, on the K-RasG12DLA2 Lung Adenocarcinoma Transgenic Mouse Model: Evaluation by Multimodality Imaging

Degrassi, Anna; Russo, Micaela; Nanni, Cristina; Patton, Veronica; Alzani, Rachele; Giusti, Anna Maria; Fanti, Stefano; Ciomei, Marina; Pesenti, Enrico; Texidó, Gemma

doi:10.1158/1535-7163.mct-09-0726

Cited by 31 publications

(23 citation statements)

References 35 publications

(37 reference statements)

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“…Inhibited tumour growth of ovarian cancer 287 and glioma xenografts 288 , KRAS G12D -induced lung cancer 289 and DMBA-induced mammary cancer 290 ; extended survival of mice bearing leukaemia 290 and intracranial glioma xenografts 288 …”

Section: Figurementioning

confidence: 99%

Cell cycle proteins as promising targets in cancer therapy

2017

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Preface Cancer is characterized by uncontrolled proliferation resulting from aberrant activity of various cell cycle proteins; therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrated that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. In contrast, many cancers are uniquely dependent on these proteins and are hence selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. Here, we review the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as future therapeutic potential of various inhibitors. We focus only on proteins that directly regulate cell cycle progression. Cyclin-dependent kinases with transcriptional functions, as well as PARP inhibitors, which are highly successful in targeting BRCA1/BRCA2-mutant tumours, are not covered by this review.

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Section: Figurementioning

confidence: 99%

Cell cycle proteins as promising targets in cancer therapy

2017

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“…MRI permits a wide variety of longitudinal studies not possible with other destructive analytical methods. Recently, MRI for tumors has become more readily available in cancer research and has been used for several transgenic models including lung (11) and ovarian tumors (6). Transgenic tumor models have been evaluated by MRI not only to assess tumor size but also to evaluate therapeutic response (6,12).…”

Section: Discussionmentioning

confidence: 99%

Adrenal tumor volume in a genetically engineered mouse model of neuroblastoma determined by magnetic resonance imaging

Kawano

Hattori

Iwakura

et al. 2012

Experimental and Therapeutic Medicine

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“…In vivo characterization of oral active compound PHA-848125 showed a dosedependent inhibition of human A2780 ovarian carcinoma xenograft tumor growth on mice up to 91%. Significant tumor growth inhibition was also observed in a K-Ras mutant lung adenocarcinoma transgenic mouse model, carcinogen-induced tumors, and in disseminated primary leukemia models (Albanese et al, 2010;Degrassi et al, 2010). Only a few details have been published for pan-Cdk inhibitor BAY 1000394 with unknown structure targeting Cdk1, Cdk2, Cdk4 and Cdk9 with high affinity (IC 50 < 10 nM) (Siemeister et al, 2010).…”

Section: Overview Of Small Molecule Cdk Inhibitors: Selectivity and Mmentioning

confidence: 99%