scholarly journals ASCT2 and LAT1 Contribution to the Hallmarks of Cancer: From a Molecular Perspective to Clinical Translation

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 203
Author(s):  
Catarina Lopes ◽  
Carina Pereira ◽  
Rui Medeiros
Keyword(s):  
Phase 1 ◽  
Clinical Applications ◽  
Selective Inhibitor ◽  
Cancer Prognosis ◽  
Amino Acid Transporters ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Cellular Energetics ◽  
Proliferative Signaling

The role of the amino acid transporters ASCT2 and LAT1 in cancer has been explored throughout the years. In this review, we report their impact on the hallmarks of cancer, as well as their clinical significance. Overall, both proteins have been associated with cell death resistance through dysregulation of caspases and sustainment of proliferative signaling through mTOR activation. Furthermore, ASCT2 appears to play an important role in cellular energetics regulation, whereas LAT1 expression is associated with angiogenesis and invasion and metastasis activation. The molecular impact of these proteins on the hallmarks of cancer translates into various clinical applications and both transporters have been identified as prognostic factors in many types of cancer. Concerning their role as therapeutic targets, efforts have been undertaken to synthesize competitive or irreversible ASCT2 and LAT1 inhibitors. However, JHP203, a selective inhibitor of the latter, is, to the best of our knowledge, the only compound included in a Phase 1 clinical trial. In conclusion, considering the usefulness of ASCT2 and LAT1 in a variety of cancer-related pathways and cancer therapy/diagnosis, the development and testing of novel inhibitors for these transporters that could be evaluated in clinical trials represents a promising approach to cancer prognosis improvement.

scholarly journals Returning to the Hallmarks of Cancer: A Brief Review and Revision

2021 ◽  
Vol 9 (2) ◽  
pp. 01-06
Author(s):  
Kaushalendra Mani Tripathi
Keyword(s):  
Drug Resistance ◽  
Genome Instability ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Different Types ◽  
Cellular Energetics ◽  
Immune Destruction ◽  
Near Future ◽  
Proliferative Signaling

The hallmarks of cancer represent principals and mechanisms on which, different types of cancers function and proliferate, These principals which also include the revised edition include sustained proliferative signaling, Evading growth suppressors , avoiding immune destruction, enabling replicative immortality, tumor promoting inflammation, activating invasion and metastasis, Inducing angiogenesis, genome instability and mutation, resisting cell death, deregulating cellular energetics. This article reviews these hallmarks and suggests any additional hallmark that can be further investigated and integrated into the revised edition , Hanahan and Weinberg’s hallmark of cancer are great pillars of understanding for modern cancer study and are open to modification , making it easily approachable ,critiqued and adds the possibility of additions in the near future. The role of exosomes are discussed with the potential to categorize drug resistance as a separate hallmark to assist us in developing therapeutics that can counter or bypass these mechanisms that assist cancer cells to proliferate even further.

scholarly journals Sweetening the hallmarks of cancer: Galectins as multifunctional mediators of tumor progression

2019 ◽  
Vol 217 (2) ◽  
Author(s):  
María Romina Girotti ◽  
Mariana Salatino ◽  
Tomás Dalotto-Moreno ◽  
Gabriel A. Rabinovich
Keyword(s):  
Immune Responses ◽  
Tumor Progression ◽  
Stromal Cells ◽  
Human Cancer ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Evolutionarily Conserved ◽  
Proliferative Signaling ◽  
Organizing Principles

Hanahan and Weinberg have proposed 10 organizing principles that enable growth and metastatic dissemination of cancer cells. These distinctive and complementary capabilities, defined as the “hallmarks of cancer,” include the ability of tumor cells and their microenvironment to sustain proliferative signaling, evade growth suppressors, resist cell death, promote replicative immortality, induce angiogenesis, support invasion and metastasis, reprogram energy metabolism, induce genomic instability and inflammation, and trigger evasion of immune responses. These common features are hierarchically regulated through different mechanisms, including those involving glycosylation-dependent programs that influence the biological and clinical impact of each hallmark. Galectins, an evolutionarily conserved family of glycan-binding proteins, have broad influence in tumor progression by rewiring intracellular and extracellular circuits either in cancer or stromal cells, including immune cells, endothelial cells, and fibroblasts. In this review, we dissect the role of galectins in shaping cellular circuitries governing each hallmark of tumors, illustrating relevant examples and highlighting novel opportunities for treating human cancer.

scholarly journals Exosomes in the Tumor Microenvironment: From Biology to Clinical Applications

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2617
Author(s):  
Vitor Rodrigues da Costa ◽  
Rodrigo Pinheiro Araldi ◽  
Hugo Vigerelli ◽  
Fernanda D’Ámelio ◽  
Thais Biude Mendes ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Biology ◽  
Clinical Applications ◽  
Future Prospects ◽  
Hallmarks Of Cancer ◽  
Cancer Heterogeneity ◽  
Important Health ◽  
Clinical Potential

Cancer is one of the most important health problems and the second leading cause of death worldwide. Despite the advances in oncology, cancer heterogeneity remains challenging to therapeutics. This is because the exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. Thus, this review aims to summarize the role of TME-derived exosomes in cancer biology and explore the clinical potential of mesenchymal stem-cell-derived exosomes as a cancer treatment, discussing future prospects of cell-free therapy for cancer treatment and challenges to be overcome.

scholarly journals Versican and Versican-matrikines in Cancer Progression, Inflammation, and Immunity

2020 ◽  
Vol 68 (12) ◽  
pp. 871-885 ◽  
Author(s):  
Athanasios Papadas ◽  
Garrett Arauz ◽  
Alexander Cicala ◽  
Joshua Wiesner ◽  
Fotis Asimakopoulos
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Immune Cell ◽  
Invasion And Metastasis ◽  
Tissue Invasion ◽  
Immune Biomarkers ◽  
Cancer Inflammation ◽  
Proliferative Signaling ◽  
Growth Suppressor

Versican is an extracellular matrix proteoglycan with key roles in multiple facets of cancer development, ranging from proliferative signaling, evasion of growth-suppressor pathways, regulation of cell death, promotion of neoangiogenesis, and tissue invasion and metastasis. Multiple lines of evidence implicate versican and its bioactive proteolytic fragments (matrikines) in the regulation of cancer inflammation and antitumor immune responses. The understanding of the dynamics of versican deposition/accumulation and its proteolytic turnover holds potential for the development of novel immune biomarkers as well as approaches to reset the immune thermostat of tumors, thus promoting efficacy of modern immunotherapies. This article summarizes work from several laboratories, including ours, on the role of this central matrix proteoglycan in tumor progression as well as tumor-immune cell cross-talk:

scholarly journals Osteopontin as a Regulator of Colorectal Cancer Progression and Its Clinical Applications

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3793
Author(s):  
Katyana Amilca-Seba ◽  
Michèle Sabbah ◽  
Annette K. Larsen ◽  
Jérôme A. Denis
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Clinical Applications ◽  
Invasion And Metastasis ◽  
Clinical Laboratories ◽  
Clinical Biomarker ◽  
Colorectal Cancer Progression ◽  
Routine Assay ◽  
Tumor Types

A high expression of the phosphoprotein osteopontin (OPN) has been associated with cancer progression in several tumor types, including breast cancer, hepatocarcinoma, ovarian cancer, and colorectal cancer (CRC). Interestingly, OPN is overexpressed in CRC and is associated with a poor prognosis linked to invasion and metastasis. Here, we review the regulation and functions of OPN with an emphasis on CRC. We examine how epigenetic and genetic regulators interact with the key signaling pathways involved in this disease. Then, we describe the role of OPN in cancer progression, including proliferation, survival, migration, invasion, and angiogenesis. Furthermore, we outline the interest of using OPN as a clinical biomarker, and discuss if and how osteopontin can be implemented as a routine assay in clinical laboratories for monitoring CRC patients. Finally, we discuss the use of OPN an attractive, but challenging, therapeutic target.

scholarly journals Implications of microRNA dysregulation in the development of prostate cancer

Reproduction ◽  
2017 ◽  
Vol 154 (4) ◽  
pp. R81-R97 ◽  
Author(s):  
Cintia Massillo ◽  
Guillermo N Dalton ◽  
Paula L Farré ◽  
Paola De Luca ◽  
Adriana De Siervi
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Small Rnas ◽  
Recent Progress ◽  
Patient Stratification ◽  
Circulating Mirnas ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Microrna Dysregulation

MicroRNAs (miRNAs) are non-coding small RNAs that target mRNA to reduce protein expression. They play fundamental roles in several diseases, including prostate cancer (PCa). A single miRNA can target hundreds of mRNAs and coordinately regulate them, which implicates them in nearly every biological pathway. Hence, miRNAs modulate proliferation, cell cycle, apoptosis, adhesion, migration, invasion and metastasis, most of them constituting crucial hallmarks of cancer. Due to these properties, miRNAs emerged as promising tools for diagnostic, prognosis and management of cancer patients. Moreover, they come out as potential targets for cancer treatment, and several efforts are being made to progress in the field of miRNA-based cancer therapy. In this review, we will summarize the recent information about miRNAs in PCa. We will recapitulate all the miRNAs involved in the androgen pathway and the biology of PCa, focusing in PCa initiation and progression. In particular, we will describe the miRNAs associated with cell proliferation, cell cycle and apoptosis in PCa, as well as invasion, adhesion and metastatic miRNAs. We will revise the recent progress made understanding the role of circulating miRNAs identified in PCa that might be useful for PCa patient stratification. Another key aspect to be discussed in this review is miRNAs’ role in PCa therapy, including the miRNAs delivery.

scholarly journals The hallmarks of cancer are also the hallmarks of wound healing

2020 ◽  
Vol 13 (648) ◽  
pp. eaay8690
Author(s):  
Lucy MacCarthy-Morrogh ◽  
Paul Martin
Keyword(s):  
Wound Healing ◽  
Cancer Progression ◽  
Tissue Repair ◽  
The Other ◽  
Molecular Processes ◽  
Hallmarks Of Cancer ◽  
Proliferative Signaling

The Hanahan and Weinberg “hallmarks of cancer” papers provide a useful structure for considering the various mechanisms driving cancer progression, and the same might be useful for wound healing. In this Review, we highlight how tissue repair and cancer share cellular and molecular processes that are regulated in a wound but misregulated in cancer. From sustained proliferative signaling and the activation of invasion and angiogenesis to the promoting role of inflammation, there are many obvious parallels through which one process can inform the other. For some hallmarks, the parallels are more obscure. We propose some new prospective hallmarks that might apply to both cancer and wound healing and discuss how wounding, as in biopsy and surgery, might positively or negatively influence cancer in the clinic.

scholarly journals The Immunobiology of Cancer: An Update Review

2017 ◽  
Vol 9 (2) ◽  
pp. 53 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Genome Instability ◽  
Neoplastic Disease ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Cancer Pathogenesis ◽  
Therapeutic Development ◽  
Solid Foundation ◽  
Proliferative Signaling ◽  
Remarkable Progress ◽  
Do So

BACKGROUND: The introduction of mechanism based targeted therapies to treat human cancers has been pledge as one of the results of three decades of remarkable progress of research into the mechanisms of cancer pathogenesis. We ponder how the description of hallmark principles is start to inform therapeutic development currently and may increasingly do so in the future.CONTENT: There are 10 biological capabilities involved as the hallmarks of cancer, during the multistep of human tumors development. These hallmarks simplify the complexities of neoplastic disease into a structured rational principles, includes sustaining proliferative signaling, eluding growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genome instability, inflammation, reprogramming energy metabolism and evading immune destruction.SUMMARY: The 10 hallmarks of cancer, in other words, the tumor’s distinctive and complementary capabilities that enable its growth and metastatic dissemination, continue to provide a solid foundation for understanding the biology of cancer. The acknowledgment of the widespread applicability of these concepts will increasingly influence the development of new manners to treat human cancer.KEYWORDS: hallmark of cancer, cancer genome, inflammation, cancer immunology, metastasis

scholarly journals Bacteria–Cancer Interface: Awaiting the Perfect Storm

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1321
Author(s):  
Jonathan Pommer Hansen ◽  
Waled Mohammed Ali ◽  
Rajeeve Sivadasan ◽  
Karthika Rajeeve
Keyword(s):  
Dna Damage ◽  
Inflammatory Response ◽  
Bacterial Infection ◽  
Close Association ◽  
Invasion And Metastasis ◽  
Epidemiological Evidence ◽  
Cellular Energetics ◽  
Immune Destruction ◽  
Perfect Storm

Epidemiological evidence reveal a very close association of malignancies with chronic inflammation as a result of persistent bacterial infection. Recently, more studies have provided experimental evidence for an etiological role of bacterial factors disposing infected tissue towards carcinoma. When healthy cells accumulate genomic insults resulting in DNA damage, they may sustain proliferative signalling, resist apoptotic signals, evade growth suppressors, enable replicative immortality, and induce angiogenesis, thus boosting active invasion and metastasis. Moreover, these cells must be able to deregulate cellular energetics and have the ability to evade immune destruction. How bacterial infection leads to mutations and enriches a tumour-promoting inflammatory response or micro-environment is still not clear. In this review we showcase well-studied bacteria and their virulence factors that are tightly associated with carcinoma and the various mechanisms and pathways that could have carcinogenic properties.

Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

2020 ◽  
Author(s):  
Shamim Mushtaq
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Web Of Science ◽  
The Body ◽  
Main Role ◽  
Hallmarks Of Cancer ◽  
Cyclin Dependent Kinases ◽  
Tumor Studies ◽  
Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

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