Role of netrin-1 and netrin-1 dependence receptors in colorectal cancers

Background: Phosphoinositide 3-kinase (PI3Ks) is a member of intracellular lipid kinases and involved in the regulation of cellular proliferation, differentiation and survival. Overexpression of the PI3K/Akt/mTOR signalling has been reported in various forms of cancers, especially in colorectal cancers (CRC). Due to their significant roles in the initiation and progression events of colorectal cancer, they are recognized as a striking therapeutic target. Objective: The present review is aimed to provide a detailed outline on the role of PI3K/Akt/mTOR pathway in the initiation and progression events of colorectal cancers as well as its function in drug resistance. Further, the role of PI3K/Akt/mTOR inhibitors alone and in combination with other chemotherapeutic drugs, in alleviating colorectal cancer is also discussed. The review contains preclinical and clinical evidence as well as patent literature of the pathway inhibitors which are natural and synthetic in origin. Methods: The data were obtained from PubMed/Medline databases, Scopus and Google patent literature. Results: PI3K/Akt/mTOR signalling is an important event in colorectal carcinogenesis. In addition, it plays significant roles in acquiring drug resistance as well as metastatic initiation events of CRCs. Several small molecules of natural and synthetic origin have been found to be potent inhibitors of CRCs by effectively downregulating the pathway. Data from various clinical studies also support these pathway inhibitors and several among them are patented. Conclusion: Inhibitors of the PI3K/mTOR pathway have been successful for the treatment of primary and metastatic colorectal cancers, rendering the pathway as a promising clinical cancer therapeutic target.

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Elevated CEA with negative PET scan on surveillance of colorectal cancers—a role of CEA kinetics

Langenbeck s Archives of Surgery ◽

10.1007/s00423-021-02352-0 ◽

2021 ◽

Author(s):

Anand Ebin Thomas ◽

Mufaddal Kazi ◽

Sanket Bankar ◽

Smruti Mokal ◽

Archi Agarwal ◽

...

Keyword(s):

Pet Scan ◽

Colorectal Cancers

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Serum YKL-40 Levels in Patients with Gastric Cancer

Biomarkers in Cancer ◽

10.4137/bic.s7154 ◽

2011 ◽

Vol 3 ◽

pp. BIC.S7154 ◽

Cited By ~ 7

Author(s):

Veyis Itik ◽

Ozgur Kemik ◽

Ahu Kemik ◽

A. Cumhur Dulger ◽

Aziz Sümer ◽

...

Keyword(s):

Gastric Cancer ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Colorectal Cancers ◽

Healthy Population ◽

Serum Samples ◽

Future Studies ◽

Male Patients

Aims and background YKL-40 is secreted by several types of tumors. Increased serum YKL-40 levels have been reported in prostate, glioblastoma, breast and colorectal cancers. Determination of YKL-40 levels may serve as a valuable biomarker for the diagnosis and treatment of gastric cancer. The purpose of this study was to determine the serum YKL-40 levels expressed in gastric carcinomas. Methods Between 2009 and 2011, we retrospectively reviewed 100 patients with gastric cancer and compared their serum samples to 75 healthy volunteers. YKL-40 levels were determined by an enzyme-linked immunosorbent assay (ELISA). Results We found significantly higher serum levels of YKL-40 in patients with gastric cancer compared to the healthy population ( P < 0.0001). We also found significant differences in serum YKL-40 levels between female and male patients with gastric cancer ( P < 0.01). Conclusions YKL-40 is over-expressed in gastric cancer, suggesting a more aggressive phenotype. YKL-40 may be a useful serum biomarker for gastric cancer identification, and future studies should focus on the role of YKL-40 in the tumorigenesis of gastric cancer and responsiveness toward treatment.

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Role of Imaging in Colorectal Cancers

Colon Polyps and Colorectal Cancer ◽

10.1007/978-3-030-57273-0_7 ◽

2020 ◽

pp. 123-151

Author(s):

Dilek Oncel

Keyword(s):

Colorectal Cancers

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Kallikrein-related peptidases and associated microRNAs as promising prognostic biomarkers in gastrointestinal malignancies

Biological Chemistry ◽

10.1515/hsz-2017-0342 ◽

2018 ◽

Vol 399 (8) ◽

pp. 821-836 ◽

Cited By ~ 6

Author(s):

Panagiotis G. Adamopoulos ◽

Panagiotis Tsiakanikas ◽

Andreas Scorilas

Keyword(s):

Wide Spectrum ◽

Prognostic Significance ◽

Prognostic Biomarkers ◽

Colorectal Cancers ◽

Gi Tract ◽

Aberrant Expression ◽

Gastrointestinal Malignancies ◽

Expression Levels ◽

Related Mortality

AbstractGastrointestinal (GI) malignancies represent a wide spectrum of diseases of the GI tract and its accessory digestive organs, including esophageal (EC), gastric (GC), hepatocellular, pancreatic (PC) and colorectal cancers (CRC). Malignancies of the GI system are responsible for nearly 30% of cancer-related morbidity and approximately 40% of cancer-related mortality, worldwide. For this reason, the discovery of novel prognostic biomarkers that can efficiently provide a better prognosis, risk assessment and prediction of treatment response is an imperative need. Human kallikrein-related peptidases (KLKs) are a subgroup of trypsin and chymotrypsin-like serine peptidases that have emerged as promising prognosticators for many human types of cancer, being aberrantly expressed in cancerous tissues. The aberrant expression ofKLKsin human malignancies is often regulated byKLK/microRNAs (miRNAs) interactions, as many miRNAs have been found to targetKLKsand therefore alter their expression levels. The biomarker utility ofKLKshas been elucidated not only in endocrine-related human malignancies, including those of the prostate and breast, but also in GI malignancies. The main purpose of this review is to summarize the existing information regarding the prognostic significance of KLKs in major types of GI malignancies and highlight the regulatory role of miRNAs on the expression levels ofKLKsin these types of cancer.

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Role of the DNA mismatch repair system in the responsiveness of metastatic colorectal cancers to chemotherapy with CPT-11 (irinotecan)

European Journal of Cancer ◽

10.1016/s0959-8049(01)81597-5 ◽

2001 ◽

Vol 37 ◽

pp. S299-S300

Author(s):

D. Fallik ◽

V. Boige ◽

F. Borrini ◽

C. Miquel ◽

J.C. Sabourin ◽

...

Keyword(s):

Mismatch Repair ◽

Dna Mismatch Repair ◽

Colorectal Cancers ◽

Repair System ◽

Dna Mismatch ◽

Dna Mismatch Repair System ◽

Mismatch Repair System

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Characterisation of heterozygous PMS2 variants in French patients with Lynch syndrome

Journal of Medical Genetics ◽

10.1136/jmedgenet-2019-106256 ◽

2020 ◽

Vol 57 (7) ◽

pp. 487-499

Author(s):

Qing Wang ◽

Julie Leclerc ◽

Gaëlle Bougeard ◽

Sylviane Olschwang ◽

Stéphanie Vasseur ◽

...

Keyword(s):

Family History ◽

Lynch Syndrome ◽

Founder Effect ◽

Predictive Value ◽

Haplotype Analysis ◽

Genomic Rearrangements ◽

Colorectal Cancers ◽

Amsterdam Criteria ◽

Insight Into

BackgroundHeterozygous germline PMS2 variants are responsible for about 5% of Lynch syndrome (LS) but their prevalence is most likely underestimated because of complicated routine screening caused by highly homologous pseudogenes. Consequently, there is limited knowledge on the implication of the PMS2 gene in LS.MethodsWe report 200 PMS2 heterozygous variants identified in 195 French patients, including 112 unique variants classified as class-3/4/5.ResultsGenomic rearrangements account for 18% of alterations. The c.137G>T variant was observed in 18% of the patients, but a founder effect could not be clearly identified by haplotype analysis. Among class-4/5 variant carriers, the median age at first tumour onset was 49 years with a predominance of colorectal (80%) and endometrial (8.1%) cancers. Seven patients developed colorectal cancers before the age of 30 with the youngest at the age of 21. Only 6.2% of class-4/5 carriers had a family history fulfilling Amsterdam I/II criteria among patients with available data. Tumours from PMS2 variant carriers exhibited microsatellite instability (96%) and loss of PMS2 expression (76%), confirming the high predictive value of somatic analysis.ConclusionOur results provide further insight into the role of the PMS2 gene in LS. While PMS2 variants are mostly detected in families not fulfilling Amsterdam criteria, which supports their lower penetrance, they can nevertheless cause early-onset cancers, highlighting the variability of their penetrance.

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