Targeting Tumour Metastasis: The Emerging Role of Nanotechnology

2020 ◽  
Vol 27 (8) ◽  
pp. 1367-1381 ◽  
Author(s):  
Sarah Visentin ◽  
Mirela Sedić ◽  
Sandra Kraljević Pavelić ◽  
Krešimir Pavelić
Keyword(s):  
Cancer Progression ◽  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Metastatic Progression ◽  
Therapeutic Concept ◽  
Molecular Alterations ◽  
Tumour Metastasis ◽  
Metastatic Cells ◽  
Metastatic Process ◽  
Underlying Mechanisms

The metastatic process has still not been completely elucidated, probably due to insufficient knowledge of the underlying mechanisms. Here, we provide an overview of the current findings that shed light on specific molecular alterations associated with metastasis and present novel concepts in the treatment of the metastatic process. In particular, we discuss novel pharmacological approaches in the clinical setting that target metastatic progression. New insights into the process of metastasis allow optimisation and design of new treatment strategies, especially in view of the fact that metastatic cells share common features with stem cells. Nano- and micro-technologies are herein elaborated in details as a promising therapeutic concept in targeted drug delivery for metastatic cancer. Progression in the field could provide a more efficient way to tackle metastasis and thus bring about advancements in the treatment and management of patients with advanced cancer.

scholarly journals Targeting the Metabolic Adaptation of Metastatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1641
Author(s):  
Josep Tarragó-Celada ◽  
Marta Cascante
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Breast Cancer Metastasis ◽  
Metabolic Inhibitors ◽  
Current Status ◽  
Metabolic Adaptation ◽  
Metastatic Cells ◽  
Colorectal Cancer Metastasis ◽  
Metastatic Process

Metabolic adaptation is emerging as an important hallmark of cancer and metastasis. In the last decade, increasing evidence has shown the importance of metabolic alterations underlying the metastatic process, especially in breast cancer metastasis but also in colorectal cancer metastasis. Being the main cause of cancer-related deaths, it is of great importance to developing new therapeutic strategies that specifically target metastatic cells. In this regard, targeting metabolic pathways of metastatic cells is one of the more promising windows for new therapies of metastatic colorectal cancer, where still there are no approved inhibitors against metabolic targets. In this study, we review the recent advances in the field of metabolic adaptation of cancer metastasis, focusing our attention on colorectal cancer. In addition, we also review the current status of metabolic inhibitors for cancer treatment.

scholarly journals Mechanisms of Metastatic Tumor Dormancy and Implications for Cancer Therapy

2019 ◽  
Vol 20 (24) ◽  
pp. 6158 ◽  
Author(s):  
Christiana M. Neophytou ◽  
Theodora-Christina Kyriakou ◽  
Panagiotis Papageorgis
Keyword(s):  
Cancer Progression ◽  
Current Knowledge ◽  
Metastatic Cancer ◽  
Metastatic Tumor ◽  
Tumor Dormancy ◽  
Secondary Site ◽  
Quiescent State ◽  
Metastatic Cells ◽  
Multistep Process ◽  
Novel Therapeutic Strategies

Metastasis, a multistep process during which tumor cells disseminate to secondary organs, represents the main cause of death for cancer patients. Metastatic dormancy is a late stage during cancer progression, following extravasation of cells at a secondary site, where the metastatic cells stop proliferating but survive in a quiescent state. When the microenvironmental conditions are favorable, they re-initiate proliferation and colonize, sometimes years after treatment of the primary tumor. This phenomenon represents a major clinical obstacle in cancer patient care. In this review, we describe the current knowledge regarding the genetic or epigenetic mechanisms that are activated by cancer cells that either sustain tumor dormancy or promote escape from this inactive state. In addition, we focus on the role of the microenvironment with emphasis on the effects of extracellular matrix proteins and in factors implicated in regulating dormancy during colonization to the lungs, brain, and bone. Finally, we describe the opportunities and efforts being made for the development of novel therapeutic strategies to combat metastatic cancer, by targeting the dormancy stage.

scholarly journals Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Kenji Ohshima ◽  
Eiichi Morii
Keyword(s):  
Oxidative Stress ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
Primary Site ◽  
Metabolic Reprogramming ◽  
Cancer Growth ◽  
Anchorage Independent Growth ◽  
Underlying Mechanisms

Cancer cells face various metabolic challenges during tumor progression, including growth in the nutrient-altered and oxygen-deficient microenvironment of the primary site, intravasation into vessels where anchorage-independent growth is required, and colonization of distant organs where the environment is distinct from that of the primary site. Thus, cancer cells must reprogram their metabolic state in every step of cancer progression. Metabolic reprogramming is now recognized as a hallmark of cancer cells and supports cancer growth. Elucidating the underlying mechanisms of metabolic reprogramming in cancer cells may help identifying cancer targets and treatment strategies. This review summarizes our current understanding of metabolic reprogramming during cancer progression and metastasis, including cancer cell adaptation to the tumor microenvironment, defense against oxidative stress during anchorage-independent growth in vessels, and metabolic reprogramming during metastasis.

scholarly journals Roles of Integrins in Gastrointestinal Cancer Metastasis

2021 ◽  
Vol 8 ◽  
Author(s):  
Sicong Hou ◽  
Jiaxin Wang ◽  
Wenqian Li ◽  
Xin Hao ◽  
Qinglei Hang
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Gastrointestinal Cancer ◽  
Cancer Metastasis ◽  
Large Family ◽  
Metastatic Progression ◽  
Cellular Behaviors ◽  
Mediate Cell Adhesion ◽  
Mediate Cell ◽  
Underlying Mechanisms

Integrins are a large family of heterodimeric transmembrane receptors which mediate cell adhesion and transmit signals to the cell interior. The mechanistic roles of integrins have long been an enigma in cancer, given its complexity in regulating different cellular behaviors. Recently, however, increasing research is providing new insights into its function and the underlying mechanisms, which collectively include the influences of altered integrin expression on the aberrant signaling pathways and cancer progression. Many studies have also demonstrated the potentiality of integrins as therapeutic targets in cancer treatment. In this review, we have summarized these recent reports and put a particular emphasis on the dysregulated expression of integrins and how they regulate related signaling pathways to facilitate the metastatic progression of gastrointestinal cancer, including gastric cancer (GC) and colorectal cancer (CRC), which will address the crucial roles of integrins in gastrointestinal cancer.

Invasion and metastasis

2016 ◽  
pp. 61-71
Author(s):  
Andrew P. Mazar ◽  
Andrey Ugolkov ◽  
Jack Henkin ◽  
Richard W. Ahn ◽  
Thomas V. O’Halloran
Keyword(s):  
New Drugs ◽  
Molecular Pathways ◽  
Cellular Interactions ◽  
Metastatic Progression ◽  
Circulating Tumour Cells ◽  
Metastatic Cells ◽  
Specific Organ ◽  
Metastatic Process ◽  
Identification And Characterization

Mortality in cancer patients usually occurs as a result of dissemination of their disease, a multi-factorial process called metastasis. This chapter discusses current understanding of how metastasis occurs and the pathways and cellular interactions that contribute to this process. Current views on lymphatic, haematogenous, and direct dissemination of metastatic cells through body cavities are considered, along with the contribution of tumour stromal cells, immune, and infiltrating cells derived from bone marrow, and angiogenesis to the metastatic process. Recent advances in characterizing metastatic niches and the contribution of specific organ sites and microenvironments to metastatic progression are presented, and the identification and characterization of circulating tumour cells and their role in metastasis are considered. Finally, representative molecular pathways as well as a sampling of new drugs in development for the treatment of metastatic disease are presented and referenced.

scholarly journals Long Non-Coding RNA HOTAIR in Breast Cancer Therapy

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1197 ◽  
Author(s):  
Monica Cantile ◽  
Maurizio Di Bonito ◽  
Margherita Cerrone ◽  
Francesca Collina ◽  
Michelino De Laurentiis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Experimental Studies ◽  
Treatment Strategies ◽  
Cancer Type ◽  
Metastatic Progression ◽  
Aberrant Expression ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Breast cancer (BC) is the most common cancer type among women, and morbidity and mortality rates are still very high. Despite new innovative therapeutic approaches for all BC molecular subtypes, the discovery of new molecular biomarkers involved in tumor progression has been fundamental for the implementation of personalized treatment strategies and improvement of patient management. Many experimental studies indicate that long non-coding RNAs (lncRNAs) are strongly involved in BC initiation, metastatic progression, and drug resistance. In particular, aberrant expression of HOX transcript antisense intergenic RNA (HOTAIR) lncRNA plays an important role in BC contributing to its progression and represents a predictor of BC metastasis. For its proven prognostic value, HOTAIR could represent a potential therapeutic target in BC. In the present review, we summarize the role of HOTAIR in cancer progression and drug resistance, in particular in BC, and we illustrate the main approaches for silencing it.

scholarly journals Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Zihe Guo ◽  
Ayao Guo ◽  
Chuang Zhou
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Treatment Strategies ◽  
Dependent Manner ◽  
Promote Cell Migration ◽  
Cancer Aggressiveness ◽  
Novel Treatment Strategies ◽  
Underlying Mechanisms

Continuous chemotherapy pressure-elicited annexin-A6 (ANXA6)-containing exosome (ANXA6-exo) secretion contributes to paclitaxel (PTX) resistance in breast cancer (BC), but the molecular mechanisms are not fully elucidated. The present study managed to investigate this issue and found that ANXA6-exo promoted PTX resistance and cancer progression in BC cells in a Yes-associated protein 1 (YAP1)-dependent manner. Specifically, the parental PTX-sensitive BC (PS-BC) cells were exposed to continuous low-dose PTX to generate PTX-resistant BC (PR-BC) cells, and we found that BC stem cells tended to be enriched in the descendent PR-BC cells in contrast with the PS-BC cells. In addition, PR-BC cell-derived exosomes were featured with highly expressed ANXA6, and ANXA6-exo delivered ANXA6 to promote cell migration, growth, autophagy, and stemness in PS-BC cells. Interestingly, ANXA6-exo increased PTX resistance in PS-BC cells via inducing autophagy, and the effects of ANXA6-exo on PTX resistance in PS-BC cells were abrogated by co-treating cells with the autophagy inhibitor 3-methyladenine. Moreover, the underlying mechanisms were uncovered, and we evidenced that ANXA6-exo up-regulated YAP1 to promote Hippo pathway dysregulation, and the promoting effects of ANXA6-exo on PTX resistance and cancer aggressiveness in BC cells were abrogated by silencing YAP1. Taken together, this study firstly elucidated the underlying mechanisms by which BCSC-derived ANXA6-exo facilitated BC progression and PTX resistance, which might help to develop novel treatment strategies for BC in clinic.

A new biomarker in monitoring breast cancer: CA 549.

1988 ◽  
Vol 6 (12) ◽  
pp. 1815-1821 ◽  
Author(s):  
R A Beveridge ◽  
D W Chan ◽  
D Bruzek ◽  
D Damron ◽  
K R Bray ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Milk Fat ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Breast Diseases ◽  
Metastatic Progression ◽  
Serum Samples ◽  
Wide Range ◽  
Milk Fat Globule Membranes

Serum biomarkers are not very reliable in assessing outcome or predicting recurrence of breast cancer. Clinically, carcinoembryonic antigen (CEA) is widely used and is elevated in a majority of patients with metastatic breast cancer. However, it is falsely elevated in a wide range of nonmalignant conditions and correlates poorly with disease progression. We evaluated a newly described monoclonal antibody, CA 549, in an immunoradiometric assay which uses two monoclonal antibodies directed against tumor and milk fat globule membranes. CA 549 and CEA were studied in 682 patients, 331 of whom had breast diseases and 99 of whom were followed with multiple serum samples. Of 69 patients with benign breast diseases, 1.5% had elevated CA 549, 0% of 30 pregnant women had elevated CA 549, and 26% of patients with nonmalignant liver disease had CA 549 elevation. In metastatic cancer of prostate, ovary, endometrium, colon, and lung CA 549 was elevated in 12% to 50% of cases with levels less than 120 U/mL. In breast cancer, CA 549 was elevated in 11% of 88 patients who received adjuvant chemotherapy and had no evidence of metastasis; in 23% of 16 patients in complete remission after chemotherapy; in 63% of 52 patients in partial remission after therapy; and in 83% of 106 patients with progression of breast cancer compared with 63% with elevated CEA (P = .001). In diseases of the breast, CA 549 has a sensitivity In diseases of the breast, CA 549 has a sensitivity and specificity of 77% and 92% v 61% and 92% for CEA. Of 99 patients serially monitored with clinically documented breast cancer progression, regression, or stability of disease, CA 549 was statistically significantly superior to CEA in monitoring a greater than 25% change in those patients with metastatic progression (P = .03). CA 549 is a new serum marker that should be control tested in prospective clinical trials alone or in conjunction with other markers.

scholarly journals Stochastic Evolution of Pancreatic Cancer Metastases During Logistic Clonal Expansion

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Kimiyo N. Yamamoto ◽  
Lin L. Liu ◽  
Akira Nakamura ◽  
Hiroshi Haeno ◽  
Franziska Michor
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Growth Models ◽  
Treatment Strategies ◽  
Evolutionary Model ◽  
Growth Patterns ◽  
Logistic Growth ◽  
Metastatic Progression ◽  
Treatment Regimens ◽  
Analytical Approximations

Despite recent progress in diagnostic and multimodal treatment approaches, most cancer deaths are still caused by metastatic spread and the subsequent growth of tumor cells in sites distant from the primary organ. So far, few quantitative studies are available that allow for the estimation of metastatic parameters and the evaluation of alternative treatment strategies. Most computational studies have focused on situations in which the tumor cell population expands exponentially over time; however, tumors may eventually be subject to resource and space limitations so that their growth patterns deviate from exponential growth to adhere to density-dependent growth models. In this study, we developed a stochastic evolutionary model of cancer progression that considers alterations in metastasis-related genes and intercellular growth competition leading to density effects described by logistic growth. Using this stochastic model, we derived analytical approximations for the time between the initiation of tumorigenesis and diagnosis, the expected number of metastatic sites, the total number of metastatic cells, the size of the primary tumor, and survival. Furthermore, we investigated the effects of drug administration and surgical resection on these quantities and predicted outcomes for different treatment regimens. Parameter values used in the analysis were estimated from data obtained from a pancreatic cancer rapid autopsy program. Our theoretical approach allows for flexible modeling of metastatic progression dynamics.

Mechanisms underlying heart failure in type 2 diabetes mellitus

2019 ◽  
pp. 37-39
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Cardio Vascular

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

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