A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer

Heijink, D. M.; Fehrmann, Rudolf S.N.; Vries, de Elisabeth G. E.; Koornstra, Jan J.; Oosterhuis, Dorenda; Zee, van der Ate; Kleibeuker, Jan H.; Jong, de Steven

doi:10.1038/onc.2010.578

Cited by 25 publications

(21 citation statements)

References 61 publications

(58 reference statements)

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“…Accordingly, the role and importance of Hh signaling pathway vary during each stage of the process 49,65. Zhang et al found that Smo and Gli1 expressions were enhanced gradually from the normal colon to colonic adenoma and then to the CRC, implying that the role of the Hh pathway may be increasingly enhanced during the process of CRC tumorigenesis 44.…”

Section: Hh Signaling Pathway In Crcmentioning

confidence: 99%

Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy

Zhu

Liu

et al. 2017

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Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide. It is a complicated and often fatal cancer, and is related to a high disease-related mortality. Around 90% of mortalities are caused by the metastasis of CRC. Current treatment statistics shows a less than 5% 5-year survival for patients with metastatic disease. The development and metastasis of CRC involve multiple factors and mechanisms. The Hedgehog (Hh) signaling plays an important role in embryogenesis and somatic development. Abnormal activation of the Hh pathway has been proven to be related to several types of human cancers. The role of Hh signaling in CRC, however, remains controversial. In this review, we will go through previous literature on the Hh signaling and its functions in the formation, proliferation, and metastasis of CRC. We will also discuss the potential of targeting Hh signaling pathway in the treatment, prognosis, and prevention of CRC.

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Section: Hh Signaling Pathway In Crcmentioning

confidence: 99%

Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy

Zhu

Liu

et al. 2017

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“…In addition, several gene expression profiles have been reported in CRC [7], [8]. Some studies also surveyed gene expression in CRA, and analyzed the lineage with CRC [9], [10], [11], [12], [13], [14]. Nevertheless, most analyses were performed from a limited number of CRA samples.…”

Section: Introductionmentioning

confidence: 99%

A Gene Expression and Pre-mRNA Splicing Signature That Marks the Adenoma-Adenocarcinoma Progression in Colorectal Cancer

et al. 2014

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It is widely accepted that most colorectal cancers (CRCs) arise from colorectal adenomas (CRAs), but transcriptomic data characterizing the progression from colorectal normal mucosa to adenoma, and then to adenocarcinoma are scarce. These transition steps were investigated using microarrays, both at the level of gene expression and alternative pre-mRNA splicing. Many genes and exons were abnormally expressed in CRAs, even more than in CRCs, as compared to normal mucosae. Known biological pathways involved in CRC were altered in CRA, but several new enriched pathways were also recognized, such as the complement and coagulation cascades. We also identified four intersectional transcriptional signatures that could distinguish CRAs from normal mucosae or CRCs, including a signature of 40 genes differentially deregulated in both CRA and CRC samples. A majority of these genes had been described in different cancers, including FBLN1 or INHBA, but only a few in CRC. Several of these changes were also observed at the protein level. In addition, 20% of these genes (i.e. CFH, CRYAB, DPT, FBLN1, ITIH5, NR3C2, SLIT3 and TIMP1) showed altered pre-mRNA splicing in CRAs. As a global variation occurring since the CRA stage, and maintained in CRC, the expression and splicing changes of this 40-gene set may mark the risk of cancer occurrence from analysis of CRA biopsies.

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“…PD has been shown preliminarily to limit disease progression in patients with inoperable RB-positive teratomas, which are commonly resistant to chemo- and radiation therapy, with minimal adverse events. 14 Importantly, clinical trials have been initiated based on pre-clinical data from both hematological and solid tumors (for example, lymphoma, 15 leukemia, 16, 17 myeloma 18, 19 , breast, 20, 21, 22, 23, 24, 25 colon, 26, 27, 28 lung, 29 esophageal 30 and glioblastoma 31, 32 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting cell cycle and hormone receptor pathways in cancer

et al. 2013

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The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability of PD to function in the presence of existing hormone-based regimens and to cooperate with ionizing radiation to further suppress cellular growth. Importantly, it was determined that PD is a critical mediator of PD action. The anti-proliferative impact of CDK4/6 inhibition was revealed through reduced proliferation and delayed growth using PCa cell xenografts. Finally, first-in-field effects of PD on proliferation were observed in primary human prostatectomy tumor tissue explants. This study shows that selective CDK4/6 inhibition, using PD either as a single-agent or in combination, hinders key proliferative pathways necessary for disease progression and that RB status is a critical prognostic determinant for therapeutic efficacy. Combined, these pre-clinical findings identify selective targeting of CDK4/6 as a bona fide therapeutic target in both early stage and advanced PCa and underscore the benefit of personalized medicine to enhance treatment response.

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A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer

Cited by 25 publications

References 61 publications

Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy

Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy

A Gene Expression and Pre-mRNA Splicing Signature That Marks the Adenoma-Adenocarcinoma Progression in Colorectal Cancer

Targeting cell cycle and hormone receptor pathways in cancer

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