The evolving role of molecular diagnosis of cancer types and subtypes: stay tuned

Cancer, one of the largest public health problems in the world, greatly endangers human health. Every country in the world faces a significant burden due to cancer. Protein post-translational modification (PTM) plays a very important role in life. PTM makes the structure of proteins more complex and the functions more perfect. Common PTM processes include methylation, acetylation, phosphorylation, glycosylation and ubiquitination. In this paper, we introduce several common types of PTMs that were discovered in recent years in various cancer types, especially the early stages of cancer, and we explore the role of related molecules in cancer screening, diagnosis, disease surveillance and prognosis. We look forward to using PTM-relevant molecules as markers for the early diagnosis of cancer, after further in-depth research and large-scale clinical trials, to contribute to the early and accurate diagnosis of cancer, thereby improving the prognosis.

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Next Generation Sequencing In Clinical Molecular Diagnosis of Cancer: A Journey towards Personalized Diagnosis and Therapeutics

10.35841/medical-oncology.1.2.76-80 ◽

2016 ◽

Vol 01 (02) ◽

Author(s):

Tridip Chatterjee

Keyword(s):

Next Generation Sequencing ◽

Molecular Diagnosis ◽

Next Generation ◽

Diagnosis Of Cancer ◽

Personalized Diagnosis ◽

Generation Sequencing

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Role of long interspersed nuclear element-1 in the regulation of chromatin landscapes and genome dynamics

Experimental Biology and Medicine ◽

10.1177/15353702211031247 ◽

2021 ◽

pp. 153537022110312

Author(s):

Kenneth S Ramos ◽

Pasano Bojang ◽

Emma Bowers

Keyword(s):

Cancer Biology ◽

Mobile Element ◽

Cancer Diagnostics ◽

Regulatory Control ◽

Full Potential ◽

Genome Dynamics ◽

Human Illness ◽

Cancer Types ◽

Stressful Environments

LINE-1 retrotransposon, the most active mobile element of the human genome, is subject to tight regulatory control. Stressful environments and disease modify the recruitment of regulatory proteins leading to unregulated activation of LINE-1. The activation of LINE-1 influences genome dynamics through altered chromatin landscapes, insertion mutations, deletions, and modulation of cellular plasticity. To date, LINE-1 retrotransposition has been linked to various cancer types and may in fact underwrite the genetic basis of various other forms of chronic human illness. The occurrence of LINE-1 polymorphisms in the human population may define inter-individual differences in susceptibility to disease. This review is written in honor of Dr Peter Stambrook, a friend and colleague who carried out highly impactful cancer research over many years of professional practice. Dr Stambrook devoted considerable energy to helping others live up to their full potential and to navigate the complexities of professional life. He was an inspirational leader, a strong advocate, a kind mentor, a vocal supporter and cheerleader, and yes, a hard critic and tough friend when needed. His passionate stand on issues, his witty sense of humor, and his love for humanity have left a huge mark in our lives. We hope that that the knowledge summarized here will advance our understanding of the role of LINE-1 in cancer biology and expedite the development of innovative cancer diagnostics and treatments in the ways that Dr Stambrook himself had so passionately envisioned.

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The Role of Extracellular Vesicles in the Development of a Cancer Stem Cell Microenvironment Niche and Potential Therapeutic Targets

Cancers ◽

10.3390/cancers13102435 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2435

Author(s):

Thomas J. Brown ◽

Victoria James

Keyword(s):

Systematic Review ◽

Tumor Microenvironment ◽

Extracellular Vesicles ◽

Multiple Cancer ◽

Therapeutic Targeting ◽

Small Component ◽

Facilitated Communication ◽

Cell Microenvironment ◽

Cancer Types

Cancer stem cells (CSCs) have increasingly been shown to be a crucial element of heterogenous tumors. Although a relatively small component of the population, they increase the resistance to treatment and the likelihood of recurrence. In recent years, it has been shown, across multiple cancer types (e.g., colorectal, breast and prostate), that reciprocal communication between cancer and the microenvironment exists, which is, in part, facilitated by extracellular vesicles (EVs). However, the mechanisms of this method of communication and its influence on CSC populations is less well-understood. Therefore, the aim of this systematic review is to determine the evidence that supports the role of EVs in the manipulation of the tumor microenvironment to promote the survival of CSCs. Embase and PubMed were used to identify all studies on the topic, which were screened using PRISMA guidelines, resulting in the inclusion of 16 studies. These 16 studies reported on the EV content, pathways altered by EVs and therapeutic targeting of CSC through EV-mediated changes to the microenvironment. In conclusion, these studies demonstrated the role of EV-facilitated communication in maintaining CSCs via manipulation of the tumor microenvironment, demonstrating the potential of creating therapeutics to target CSCs. However, further works are needed to fully understand the targetable mechanisms upon which future therapeutics can be based.

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miR-205 in Breast Cancer: State of the Art

International Journal of Molecular Sciences ◽

10.3390/ijms22010027 ◽

2020 ◽

Vol 22 (1) ◽

pp. 27

Author(s):

Ilaria Plantamura ◽

Alessandra Cataldo ◽

Giulia Cosentino ◽

Marilena V. Iorio

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Normal Breast ◽

Response To Therapy ◽

Aberrant Expression ◽

Open Questions ◽

Tumor Tissues ◽

Breast Physiology ◽

Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

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Non-Coding RNAs as Prognostic Markers for Endometrial Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22063151 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3151 ◽

Cited By ~ 2

Author(s):

Roberto Piergentili ◽

Simona Zaami ◽

Anna Franca Cavaliere ◽

Fabrizio Signore ◽

Giovanni Scambia ◽

...

Keyword(s):

Endometrial Cancer ◽

Prognostic Markers ◽

Classification Systems ◽

Prognostic Role ◽

Protein Coding ◽

Pathological Characteristics ◽

Epigenetic Events ◽

Cancer Types ◽

Non Coding Rnas

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

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Histone Modifying Enzymes in Gynaecological Cancers

Cancers ◽

10.3390/cancers13040816 ◽

2021 ◽

Vol 13 (4) ◽

pp. 816

Author(s):

Priya Ramarao-Milne ◽

Olga Kondrashova ◽

Sinead Barry ◽

John D. Hooper ◽

Jason S. Lee ◽

...

Keyword(s):

Genome Instability ◽

Cpg Islands ◽

Gene Promoter ◽

Driver Mutations ◽

Promoter Regions ◽

Post Translational Modifications ◽

Chromatin Dynamics ◽

Cancer Types ◽

Histone Modifying Enzymes

Genetic and epigenetic factors contribute to the development of cancer. Epigenetic dysregulation is common in gynaecological cancers and includes altered methylation at CpG islands in gene promoter regions, global demethylation that leads to genome instability and histone modifications. Histones are a major determinant of chromosomal conformation and stability, and unlike DNA methylation, which is generally associated with gene silencing, are amenable to post-translational modifications that induce facultative chromatin regions, or condensed transcriptionally silent regions that decondense resulting in global alteration of gene expression. In comparison, other components, crucial to the manipulation of chromatin dynamics, such as histone modifying enzymes, are not as well-studied. Inhibitors targeting DNA modifying enzymes, particularly histone modifying enzymes represent a potential cancer treatment. Due to the ability of epigenetic therapies to target multiple pathways simultaneously, tumours with complex mutational landscapes affected by multiple driver mutations may be most amenable to this type of inhibitor. Interrogation of the actionable landscape of different gynaecological cancer types has revealed that some patients have biomarkers which indicate potential sensitivity to epigenetic inhibitors. In this review we describe the role of epigenetics in gynaecological cancers and highlight how it may exploited for treatment.

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The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review

Cancers ◽

10.3390/cancers13163949 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3949

Author(s):

Federica Rascio ◽

Federica Spadaccino ◽

Maria Teresa Rocchetti ◽

Giuseppe Castellano ◽

Giovanni Stallone ◽

...

Keyword(s):

Drug Resistance ◽

Akt Pathway ◽

Invasion And Metastasis ◽

Pathogenic Role ◽

Multiple Cancer ◽

Downstream Target ◽

Cancer Types ◽

Multi Level ◽

Survival Mechanisms

The PI3K/AKT pathway is one of the most frequently over-activated intracellular pathways in several human cancers. This pathway, acting on different downstream target proteins, contributes to the carcinogenesis, proliferation, invasion, and metastasis of tumour cells. A multi-level impairment, involving mutation and genetic alteration, aberrant regulation of miRNAs sequences, and abnormal phosphorylation of cascade factors, has been found in multiple cancer types. The deregulation of this pathway counteracts common therapeutic strategies and contributes to multidrug resistance. In this review, we underline the involvement of this pathway in patho-physiological cell survival mechanisms, emphasizing its key role in the development of drug resistance. We also provide an overview of the potential inhibition strategies currently available.

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Role of the NUDT Enzymes in Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22052267 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2267

Author(s):

Roni H. G. Wright ◽

Miguel Beato

Keyword(s):

Breast Cancer ◽

Signaling Pathways ◽

Cancer Progression ◽

Breast Cancers ◽

Metastatic Colonization ◽

Hormone Receptor Positive ◽

Aggressive Cancer ◽

Cancer Types ◽

Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

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RegulatING chromatin regulators: post-translational modification of the ING family of epigenetic regulators

Biochemical Journal ◽

10.1042/bj20121632 ◽

2013 ◽

Vol 450 (3) ◽

pp. 433-442 ◽

Cited By ~ 8

Author(s):

Shankha Satpathy ◽

Arash Nabbi ◽

Karl Riabowol

Keyword(s):

Biological Significance ◽

Type Ii ◽

Post Translational Modification ◽

Post Translational Modifications ◽

Chromatin Regulators ◽

Cancer Types ◽

Splicing Isoforms ◽

Enrichment Techniques ◽

Affect Cell Growth

The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of PTMs (post-translational modifications) of INGs is important in understanding how ING functions are fine-tuned in the physiological setting and how they add to the repertoire of activities affected by the INGs. In the present paper we review the different PTMs that have been reported to occur on INGs. We discuss the PTMs that modulate ING function under normal conditions and in response to a variety of stresses. We also describe the ING PTMs that have been identified by several unbiased MS-based PTM enrichment techniques and subsequent proteomic analysis. Among the ING PTMs identified to date, a subset has been characterized for their biological significance and have been shown to affect processes including subcellular localization, interaction with enzymatic complexes and ING protein half-life. The present review aims to highlight the emerging role of PTMs in regulating ING function and to suggest additional pathways and functions where PTMs may effect ING function.

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