5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future

Vodenková, Soňa; Büchler, Tomáš; Červená, Klára; Veškrňová, Veronika; Vodicka, Pavel; Vymetalková, Veronika

doi:10.1016/j.pharmthera.2019.107447

Cited by 590 publications

(442 citation statements)

References 249 publications

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“…The CSCs share several normal stem cells features that provide a long existence, including the relative silence, dormancy, resistance to chemotherapeutic agents and toxins through the expression of drug efflux transporters, an active DNA-repair capacity and a resistance to apoptosis, vascular niche, stability to hypoxia, and enhanced activity of repair enzymes [ 71 ]. Understanding the characteristics of CSCs is crucial to lay the foundation for new generation in treatment of cancer and their identifying and eliminating represents a significant help to diminish drug resistance [ 72 ].…”

Section: The Cancer Stem Cell Modelmentioning

confidence: 99%

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Filip

Vymetalková

Petera

et al. 2020

IJMS

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Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC). In this review, we overview possible molecular and clinicopathological biomarkers that may provide prognostic and predictive information for patients with distant metastasis. These may comprise sidedness of the tumor, molecular profile and epigenetic characteristics of the primary tumor and arising metastatic CRC, and early markers reflecting cancer cell resistance in mCRC and biomarkers identified from transcriptome. This review discusses current stage in employment of these biomarkers in clinical practice as well as summarizes current experience in identifying predictive biomarkers in mCRC treatment.

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Section: The Cancer Stem Cell Modelmentioning

confidence: 99%

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Filip

Vymetalková

Petera

et al. 2020

IJMS

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“…The therapy of CRC has comprehensively been reviewed [38,123]. Despite all the efforts in CRC therapy over the years, 5-year survival remains unsatisfactory.…”

Section: Possible Utilization Of Oxidative Dna Damage In Colorectal Cmentioning

confidence: 99%

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

Vodička

Urbanová

Makovický

et al. 2020

IJMS

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Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.

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“…The majority of the patients receiving chemotherapy will eventually experience tumor recurrence due to drug resistance, and this has become a key barrier for the clinical treatment of colorectal cancer. 5,6 Thus, revealing the underlying mechanism of colorectal tumorigenesis and identify novel therapeutic targets are necessary for the development of effective therapies for CRC patients.…”

Section: Introductionmentioning

confidence: 99%

<p>Inhibition of ERKs/Akt-Mediated c-Fos Expression Is Required for Piperlongumine-Induced Cyclin D1 Downregulation and Tumor Suppression in Colorectal Cancer Cells</p>

Gao

Zhou

et al. 2020

OTT

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Background: Deregulation of Cyclin D1 and cell cycle progression plays a critical role in tumorigenesis. The natural compound piperlongumine (PL) exhibits potential anticancer effects in various cancer models, but the underlying mechanism needs further elucidation. Methods: The inhibitory effect of PL on colorectal cancer (CRC) cells was determined by anchorage-dependent and-independent assays. The protein level of Cyclin D1 was examined by immunoblot (IB) and immunohistochemical staining (IHC). The mRNA level was determined by qRT-PCR. Phosphorylation of histone H3 was analyzed by immunofluorescence (IF). The cell cycle was examined by flow cytometry. The in vivo antitumor effect was validated by the xenograft mouse model. Results: Cyclin D1 was overexpressed in CRC tissues and cells, and was required for maintaining cell growth, colony formation, and in vivo tumorigenesis. PL decreased the protein level of c-Fos, which eventually reduced the transcriptional activity of AP-1 and the mRNA level of Cyclin D1. Mechanism study showed that PL impaired EGF-induced activation of ERK1/2 and Akt signalings, which resulted in a reduction of c-Fos transcription. Furthermore, PL reduced the half-life of c-Fos and caused the ubiquitination-dependent degradation of c-Fos. Finally, the in vivo antitumor effect of PL on CRC cells was examined using a xenograft mouse model. Conclusion: Our data indicate that PL is a promising antitumor agent that deserves further study for CRC treatment.

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5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future

Cited by 590 publications

References 249 publications

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

<p>Inhibition of ERKs/Akt-Mediated c-Fos Expression Is Required for Piperlongumine-Induced Cyclin D1 Downregulation and Tumor Suppression in Colorectal Cancer Cells</p>

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