scholarly journals The Complexity of Colorectal Cancer Biology — Putting Bricks on the Path to Personalized Medicine

Author(s):  
Emilia Balboa ◽  
Angel Carracedo ◽  
Francisco Barros
2020 ◽  
Vol 27 (17) ◽  
pp. 2779-2791 ◽  
Author(s):  
Anna Nappi ◽  
Guglielmo Nasti ◽  
Carmela Romano ◽  
Massimiliano Berretta ◽  
Alessandro Ottaiano

: Colorectal cancer represents the third most frequently occurring cancer worldwide. In the last decade, the survival of patients affected by metastatic colorectal cancer (mCRC) has improved through the introduction of biological drugs. However, in this new and dynamic therapeutic context, research about prognostic and predictive factors is important to guide the oncologists to effective therapies as well as to improve the understanding of colorectal cancer biology. Their identification is an intensive area of research and our future goal will be to depict tumour-specific "molecular signatures" in order to predict the clinical course of the disease and the best treatments. : In this report, we describe clinical, pathological and molecular biomarkers that can play a role as prognostic or predictive factors in mCRC.


2021 ◽  
Vol 11 (6) ◽  
pp. 535
Author(s):  
Bader Almuzzaini ◽  
Jahad Alghamdi ◽  
Alhanouf Alomani ◽  
Saleh AlGhamdi ◽  
Abdullah A. Alsharm ◽  
...  

Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. Discovery of novel variants in local population provides confident targets for developing biomarkers for personalized medicine. We identified the need to generate high-quality sequencing data from local colorectal cancer patients and understand the pattern of occurrence of variants. In this report, we used archived samples from Saudi Arabia and used the AmpliSeq comprehensive cancer panel to identify novel somatic variants. We report a comprehensive analysis of next-generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity, and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in the large intestine. APC, RET, and EGFR genes were most frequently mutated. A higher number of variants were identified in the left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.


2021 ◽  
Vol 16 (1) ◽  
pp. 523-536
Author(s):  
Minghao Li ◽  
Jianbin Zhuang ◽  
Di Kang ◽  
Yuzhuo Chen ◽  
Weiliang Song

Abstract Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.


Author(s):  
Pieter-Jan van Dam ◽  
Steven Van Laere

Recent efforts by worldwide consortia such as The Cancer Genome Atlas and the International Cancer Genome Consortium have greatly accelerated our knowledge of human cancer biology. Nowadays, complete sets of human tumours that have been characterized at the genomic, epigenomic, transcriptomic, or proteomic level are available to the research community. The generation of these data was made possible thanks to the application of high-throughput molecular profiling techniques such as microarrays and next-generation sequencing. The primary conclusion from current profiling experiments is that human cancer is a complex disease characterized by extreme molecular heterogeneity, both between and within the classical, tissue-defined cancer types. This molecular variety necessitates a paradigm shift in patient management, away from generalized therapy schemes and towards more personalized treatments. This chapter provides an overview of how molecular cancer profiling can assist in facilitating this transition. First, the state-of-the-art of molecular breast cancer profiling is reviewed to provide a general background. Then, the most pertinent high-throughput molecular profiling techniques along with various data mining techniques (i.e. unsupervised clustering, statistical learning) are discussed. Finally, the challenges and perspectives with respect to molecular cancer profiling, also from the perspective of personalized medicine, are summarized.


2019 ◽  
Vol 62 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Hanumant Chouhan ◽  
Sylvain Ferrandon ◽  
Jennifer DeVecchio ◽  
Matthew F. Kalady ◽  
James M. Church

2019 ◽  
Vol 3 (1) ◽  
pp. 223-234 ◽  
Author(s):  
Hans Clevers ◽  
David A. Tuveson

Organoid cultures have emerged as powerful model systems accelerating discoveries in cellular and cancer biology. These three-dimensional cultures are amenable to diverse techniques, including high-throughput genome and transcriptome sequencing, as well as genetic and biochemical perturbation, making these models well suited to answer a variety of questions. Recently, organoids have been generated from diverse human cancers, including breast, colon, pancreas, prostate, bladder, and liver cancers, and studies involving these models are expanding our knowledge of the etiology and characteristics of these malignancies. Co-cultures of cancer organoids with non-neoplastic stromal cells enable investigation of the tumor microenvironment. In addition, recent studies have established that organoids have a place in personalized medicine approaches. Here, we describe the application of organoid technology to cancer discovery and treatment.


2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Valentin Vautrot ◽  
Gaëtan Chanteloup ◽  
Mohammed Elmallah ◽  
Marine Cordonnier ◽  
François Aubin ◽  
...  

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths worldwide. Tumor microenvironment (TME) contains many cell types including stromal cells, immune cells, and endothelial cells. The TME modulation explains the heterogeneity of response to therapy observed in patients. In this context, exosomes are emerging as major contributors in cancer biology. Indeed, exosomes are implicated in tumor proliferation, angiogenesis, invasion, and premetastatic niche formation. They contain bioactive molecules such as proteins, lipids, and RNAs. More recently, many studies on exosomes have focused on miRNAs, small noncoding RNA molecules able to influence protein expression. In this review, we describe miRNAs transported by exosomes in the context of CRC and discuss their influence on TME and their potential as circulating biomarkers. This overview underlines emerging roles for exosomal miRNAs in cancer research for the near future.


2017 ◽  
Vol 32 (7) ◽  
pp. 1077-1084 ◽  
Author(s):  
R. Aarnoutse ◽  
J. M. P. G. M. de Vos-Geelen ◽  
J. Penders ◽  
E. G. Boerma ◽  
F. A. R. M. Warmerdam ◽  
...  

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