Target genetic abnormalities for the treatment of colon cancer and its progression to metastasis

2020 ◽  
Vol 21 ◽  
Author(s):  
Tushar Baviskar ◽  
Munira Momin ◽  
Jingwen Liu ◽  
Bin Guo ◽  
Lokesh Bhatt
Keyword(s):  
Colon Cancer ◽  
Chromosomal Abnormalities ◽  
Treatment Options ◽  
Genetic Alterations ◽  
Vital Role ◽  
Colorectal Carcinogenesis ◽  
Tumour Suppressor Genes ◽  
Genetic Abnormalities ◽  
P53 Genes

: Colorectal carcinogenesis involves various processes from the accumulation of genetic alterations to genetic and epigenetic modulations and chromosomal abnormalities. It also involves mutations in oncogenes and tumour suppressor genes. Genomic instability plays a vital role in CRC. Advances in modern biological techniques and molecular level studies have identified various genes that are involved in colorectal cancer (CRC). KRAS, BRAF, PI3K, and p53 genes play a significant role in different phases of CRC. Alteration of these genes leads to development or progression and metastasis colon cancer. This review focuses on the role of KRAS, BRAF, PI3KCA, and TP53 genes in carcinogenesis and their significance in various stages of CRC. It also provides insights on specific modulators acting on these genes. Further, this review discusses the mechanism of the pathways involving these genes in carcinogenesis and current molecules and treatment options under various stages of clinical evaluation.

Nutrigenomics and Life Style Facet- A Modulatory Molecular Evidence in Progression of Breast and Colon Cancer with Emerging Importance

2021 ◽  
Vol 21 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Colon Cancer ◽  
Molecular Mechanisms ◽  
Health Management ◽  
Vital Role ◽  
Molecular Evidence ◽  
Nutritional Interventions ◽  
Phenotypic Alteration ◽  
The Individual ◽  
Supplement Intake

: Legitimate nutrition assumes a significant role in preventing diseases and, in this way, nutritional interventions establish vital strategies in the area of public health. Nutrigenomics centres on the different genes and diet in an individual and how an individual’s genes influence the reaction to bioactive foodstuff. It targets considering the genetic and epigenetic interactions with nutrients to lead to a phenotypic alteration and consequently to metabolism, differentiation, or even apoptosis. Nutrigenomics and lifestyle factors play a vital role in health management and represent an exceptional prospect for the improvement of personalized diets to the individual at risk of developing diseases like cancer. Concerning cancer as a multifactorial genetic ailment, several aspects need to be investigated and analysed. Various perspectives should be researched and examined regarding the development and prognosis of breast and colon cancer. Malignant growth occurrence is anticipated to upsurge in the impending days, and an effective anticipatory strategy is required. The effect of dietary components, basically studied by nutrigenomics, looks at gene expression and molecular mechanisms. It also interrelates bioactive compounds and nutrients because of different 'omics' innovations. Several preclinical investigations demonstrate the pertinent role of nutrigenomics in breast and colon cancer, and change of dietary propensities is conceivably a successful methodology for reducing cancer risk. The connection between the genomic profile of patients with breast or colon cancer and their supplement intake, it is conceivable to imagine an idea of personalized medicine, including nutrition and medicinal services.

scholarly journals Role of Enzymes in Causing Neurological Disorders

2021 ◽  
Vol 12 (1) ◽  
pp. 466-476
Author(s):  
Vysakh Visweswaran ◽  
Roshni PR
Keyword(s):  
Neurological Disorders ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Direct Result ◽  
Permanent Disability ◽  
Genetic Abnormalities ◽  
Underlying Pathology

Diseases of the nervous system are always associated with poor prognosis and limited treatment options. The fragile nature of the neurons and their inability to replicate means that neurological disorders are associated with a permanent disability. Pharmacotherapy of neurological diseases requires understanding the molecular mechanisms involved in the disease pathology. In most of the cases a faulty cellular biochemical pathway is involved, resulting from a defective enzyme. This article focusses on role of enzymes in various neurological disorders. To review pertinent literature and summarise the role of enzymes in the underlying pathology of various neurological disorders. A comprehensive literature search was conducted using PubMed, SCOPUS, J-GATE and Google Scholar and relevant papers were collected using the keywords enzymes, Alzheimer's disease, redox, thiamine, depression, neurotransmitters, epileptogenesis. The literature review highlighted the role of enzymes in major neurological disorders and their potential to be used as drug targets and biomarkers. Identifying defective enzymes gives us new molecular targets to focus on for developing more effective pharmacotherapeutic options. They can be also considered as potential biomarkers. An abnormal enzyme is most often a direct result of an underlying genetic abnormality. Identifying and screening for these genetic abnormalities can be used in early identification and prevention of disease in individuals who have a genetic predisposition. The modern advances in genetic engineering shows a lot of promise in correcting these abnormalities and development of revolutionary cures although ethical concerns remain. 

Antioxidant Agents and Colorectal Carcinogenesis: Role of β-Carotene, Vitamin E and Vitamin C

1996 ◽  
Vol 82 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Giuseppe Pappalardo ◽  
Antonio Guadalaxara ◽  
Giuseppe Maiani ◽  
Giovanni Illomei ◽  
Mauro Trifero ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin E ◽  
Vitamin C ◽  
Colonic Mucosa ◽  
Genetic Alterations ◽  
Colorectal Carcinogenesis ◽  
Normal Colonic Mucosa ◽  
Antioxidant Agents ◽  
Β Carotene

In consideration of findings reported in the literature and of our study, we examined the correlation between antioxidants (β-carotene, vitamin C, vitamin E) and colorectal carcinogenesis. Although diagnostic progress has been made in the last decades, no significant improvements in death rates have been achieved in the western world. Exogenous factors might be responsible for a complex alteration process of normal colonic mucosa into adenoma and carcinoma. Free radicals and reactive oxygen metabolites, due to increased production or to reduced inactivation, following a decrease in the antioxidant burden in the mucosa, might cause damage to DNA, thereby resulting in genetic alterations. This might represent the cause of the transformation process: normal mucosa→ adenoma→ carcinoma. In a prospective study, we observed a reduction of β-carotene levels in normal colonic mucosa in patients with polyps and colorectal cancer. We also showed that β-carotene supplementation raises levels of this micronutrient in the colonic mucosa of these patients. Findings from the literature and our trials show a significant decrease in the antioxidant capacity of colorectal mucosa in patients affected by colorectal cancer, although there is a significant interindividual variability. Such results suggest a possible chemopreventive role of antioxidant agents in colorectal cancer.

The role of the Wnt signalling pathway in colorectal tumorigenesis

2005 ◽  
Vol 33 (4) ◽  
pp. 672-675 ◽  
Author(s):  
J. Behrens
Keyword(s):  
Wnt Pathway ◽  
Genetic Alterations ◽  
Wnt Signalling ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Colorectal Tumorigenesis ◽  
Constitutive Activation

Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes. Mutations in the tumour suppressor APC (adenomatous polyposis coli) genes occur early in the development of CRC and lead to the stabilization of the Wnt pathway component β-catenin and to the constitutive activation of Wnt signalling. Stabilizing mutations of β-catenin can also lead to its accumulation, qualifying β-catenin as a proto-oncogene. Here I will summarize the biochemical interactions occurring in Wnt signalling and describe how alterations in Wnt pathway components lead to CRC.

scholarly journals Genetic Abnormalities in ALL

2021 ◽  
Author(s):  
Bendari Mounia ◽  
Sofia Sraidi ◽  
Nisrine Khoubila
Keyword(s):  
Chromosomal Abnormalities ◽  
Lymphoblastic Leukemia ◽  
World Health ◽  
Fish Analysis ◽  
Genetic Modifications ◽  
Genetic Abnormalities ◽  
The World ◽  
Therapeutic Protocols ◽  
Health Organization

Acute lymphoblastic leukemia (ALL), can be defined by a family of genetically heterogeneous lymphoid neoplasms derived from B- and T-lymphoid progenitors. ALL constitutes the most common childhood cancer, due to an overproduction of immature lymphoid hematopoietic cells. Genetic analyzes currently provides important information for classifying patients into prognostic groups, genetic analysis also helps to understand the mechanisms of relapse, pharmacogenetics and the development of new potential therapeutic targets, which should help to further improve the results of leukemia. In fact, the new techniques in molecular cytogenetic permits to identify new cryptic abnormalities, these discoveries have led to the development of new therapeutic protocols. The role of cytogenetic analysis is crucial on ALL patient’s management. Karyotyping coupled with FISH analysis identifies recurrent chromosomal abnormalities in ALL, many of these abnormalities have prognostic and treatment impact. This chapter summarizes chromosomal abnormalities that are common and classify ALL according to the World Health Organization (WHO) classifications (2016 revision). We will present the main genetic modifications recently identified as well as the sequence mutations which have helped in the elucidation of the pathogenesis of ALL.

Breast cancer: understanding etiology, addressing molecular signaling pathways, identifying therapeutic targets and strategizing the treatment

2021 ◽  
Vol 12 (3) ◽  
pp. 1757-1769
Author(s):  
Preeti Tanaji Mane ◽  
Sangram Prakash Patil ◽  
Balaji Sopanrao Wakure ◽  
Pravin Shridhar Wakte
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Treatment Options ◽  
Current Treatment ◽  
Vital Role ◽  
Molecular Signaling ◽  
Breast Tumorigenesis ◽  
Non Coding Rnas ◽  
Cycle Regulation

Breast cancer has messed the life of a greater number of women being the most common cancer affecting them worldwide. A number of risk factors contribute the breast malignancy, however, genetic drift is accountable the most. Depending on the cell origin, invasiveness and receptors involved, breast cancer is classified into various subtypes. The accurate diagnosis of breast cancer is important as it defines the prognosis and directs the type of treatment required. A number of major signaling pathways involved in breast tumorigenesis and its development include estrogen receptors (ERs), HER2, Wnt/β-catenin, Notch, Hedgehog (Hh), PI3K and mTOR pathway. Furthermore, certain enzymes like Cyclin dependent kinases and breast tumor kinases also play a vital role in cell cycle regulation and therefore, in the development of breast neoplasms. Recent studies have also enlightened the role of non-coding RNAs in breast cancer development. This review discusses various aspects of breast cancer such as its etiology, subtypes, various signaling pathways involved, targets projected by these pathways and the current treatment options based on a few of these targets. Also, the role of different genes, enzymes and non-coding RNAs related to breast tumorigenesis and development is discussed.

scholarly journals The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 988 ◽  
Author(s):  
Fuhr ◽  
Abreu ◽  
Carbone ◽  
El-Athman ◽  
Bianchi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Malignant Transformation ◽  
Biological Clock ◽  
Benign Tumour ◽  
Colorectal Carcinogenesis ◽  
Tumour Stroma ◽  
Colon Cancer Cells ◽  
Colorectal Tumour

Cancer cells interrelate with the bordering host microenvironment that encompasses the extracellular matrix and a nontumour cellular component comprising fibroblasts and immune-competent cells. The tumour microenvironment modulates cancer onset and progression, but the molecular factors managing this interaction are not fully understood. Malignant transformation of a benign tumour is among the first crucial events in colorectal carcinogenesis. The role of tumour stroma fibroblasts is well-described in cancer, but less well-characterized in benign tumours. In the current work we utilized fibroblasts isolated from tubulovillous adenoma, which has high risk for malignant transformation, to study the interaction between benign tumour stroma and the circadian clock machinery. We explored the role of the biological clock in this interplay taking advantage of an experimental model, represented by the co-culture of colon cancer cells with normal fibroblasts or tumour-associated fibroblasts, isolated from human colorectal tumour specimens. When co-cultured with tumour-associated fibroblasts, colon cancer cells showed alterations in their circadian and metabolic parameters, with decreased apoptosis, increased colon cancer cell viability, and increased resistance to chemotherapeutic agents. In conclusion, the interactions among colon cancer cells and tumour-associated fibroblasts affect the molecular clockwork and seem to aggravate malignant cell phenotypes, suggesting a detrimental effect of this interplay on cancer dynamics.

scholarly journals Genetics of human female infertility†

2019 ◽  
Vol 101 (3) ◽  
pp. 549-566 ◽  
Author(s):  
Svetlana A Yatsenko ◽  
Aleksandar Rajkovic
Keyword(s):  
Reproductive Organs ◽  
Genetic Alterations ◽  
Reproductive Age ◽  
Large Chromosome ◽  
Functional Development ◽  
Early Embryonic Lethality ◽  
Sequence Variations ◽  
Genetic Abnormalities ◽  
Wide Range

AbstractAbout 10% of women of reproductive age are unable to conceive or carry a pregnancy to term. Female factors alone account for at least 35% of all infertility cases and comprise a wide range of causes affecting ovarian development, maturation of oocytes, and fertilization competence, as well as the potential of a fertilized egg for preimplantation development, implantation, and fetal growth. Genetic abnormalities leading to infertility in females comprise large chromosome abnormalities, submicroscopic chromosome deletion and duplications, and DNA sequence variations in the genes that control numerous biological processes implicated in oogenesis, maintenance of ovarian reserve, hormonal signaling, and anatomical and functional development of female reproductive organs. Despite the great number of genes implicated in reproductive physiology by the study of animal models, only a subset of these genes is associated with human infertility. In this review, we mainly focus on genetic alterations identified in humans and summarize recent knowledge on the molecular pathways of oocyte development and maturation, the crucial role of maternal-effect factors during embryogenesis, and genetic conditions associated with ovarian dysgenesis, primary ovarian insufficiency, early embryonic lethality, and infertility.

scholarly journals Cell Heterogeneity and Phenotypic Plasticity in Metastasis Formation: The Case of Colon Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1368 ◽  
Author(s):  
Miriam Teeuwssen ◽  
Riccardo Fodde
Keyword(s):  
Colon Cancer ◽  
Phenotypic Plasticity ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Genetic Alterations ◽  
Primary Site ◽  
Metastasis Formation ◽  
Mesenchymal Transition ◽  
Intermediate Phenotypes

The adenoma-to-carcinoma progression in colon cancer is driven by a sequential accumulation of genetic alterations at specific tumor suppressors and oncogenes. In contrast, the multistage route from the primary site to metastasis formation is underlined by phenotypic plasticity, i.e., the capacity of disseminated tumor cells to undergo transiently and reversible transformations in order to adapt to the ever-changing environmental contexts. Notwithstanding the considerable body of evidence in support of the role played by epithelial-to-mesenchymal transition (EMT)/mesenchymal-to-epithelial transition (MET) in metastasis, its rate-limiting function, the detailed underlying cellular and molecular mechanisms, and the extension of the necessary morphologic and epigenetic changes are still a matter of debate. Rather than leading to a complete epithelial or mesenchymal state, the EMT/MET-program generates migrating cancer cells displaying intermediate phenotypes featuring both epithelial and mesenchymal characteristics. In this review, we will address the role of colon cancer heterogeneity and phenotypic plasticity in metastasis formation and the contribution of EMT to these processes. The alleged role of hybrid epithelial/mesenchymal (E/M) in collective and/or single-cell migration during local dissemination at the primary site and more systemic spreading will also be highlighted.

scholarly journals Molecular Activation of the Kv11.1 Channel Reprograms EMT in Colon Cancer by Inhibiting TGFβ Signaling via Activation of Calcineurin

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6025
Author(s):  
Najmeh Eskandari ◽  
Vitalyi Senyuk ◽  
Jennifer Moore ◽  
Zane Kalik ◽  
Qiyue Luan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Vital Role ◽  
Colon Cancer Cells ◽  
Strong Inhibition ◽  
Tgfβ Signaling ◽  
Mesenchymal Transition ◽  
Stimulation Of

Control of ionic gradients is critical to maintain cellular homeostasis in both physiological and pathological conditions, but the role of ion channels in cancer cells has not been studied thoroughly. In this work we demonstrated that activity of the Kv11.1 potassium channel plays a vital role in controlling the migration of colon cancer cells by reversing the epithelial-to-mesenchymal transition (EMT) into the mesenchymal-to-epithelial transition (MET). We discovered that pharmacological stimulation of the Kv11.1 channel with the activator molecule NS1643 produces a strong inhibition of colon cancer cell motility. In agreement with the reversal of EMT, NS1643 treatment leads to a depletion of mesenchymal markers such as SNAIL1, SLUG, TWIST, ZEB, N-cadherin, and c-Myc, while the epithelial marker E-cadherin was strongly upregulated. Investigating the mechanism linking Kv11.1 activity to reversal of EMT into MET revealed that stimulation of Kv11.1 produced a strong and fast inhibition of the TGFβ signaling. Application of NS1643 resulted in de-phosphorylation of the TGFβ downstream effectors R-SMADs by activation of the serine/threonine phosphatase PP2B (calcineurin). Consistent with the role of TGFβ in controlling cancer stemness, NS1643 also produced a strong inhibition of NANOG, SOX2, and OCT4 while arresting the cell cycle in G0/G1. Our data demonstrate that activation of the Kv11.1 channel reprograms EMT into MET by inhibiting TGFβ signaling, which results in inhibition of motility in colon cancer cells.

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