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.

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 Tumor cell dormancy as an adaptive cell stress response mechanism

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2134 ◽  
Author(s):  
Laura Vera-Ramirez ◽  
Kent W. Hunter
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Residual Disease ◽  
Tumor Dormancy ◽  
Therapeutic Interventions ◽  
Quiescent State ◽  
Metastatic Site ◽  
Cell Stress Response ◽  
Cell Dormancy ◽  
Kinetics Of

Metastases are responsible for most cancer-related deaths. The kinetics of tumor relapse is highly heterogeneous, ranging from recurrences shortly after diagnosis to years or even decades after the initial treatment. This subclinical period is known as tumor dormancy, in which residual disease remains in an undetectable state before finally appearing as an overtly proliferative metastasis. Despite recent advances in our understanding of the molecular mechanisms leading to tumor dormancy, it is still a poorly understood phase of cancer progression, which limits opportunities for the design of successful therapeutic interventions. The influence of the tumor microenvironment at the metastatic site and anti-metastatic immune responses have been shown to play a crucial role in the onset and maintenance of metastatic dormancy. However, there is still a significant gap in our understanding of how dormant cells remain viable in a quiescent state for long periods of time. Here, we review the latest experimental evidence shedding light on the biological processes that enable dormant tumor cells to endure the multiple stresses encountered at the metastatic site.

scholarly journals Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 114
Author(s):  
Lisa Linck-Paulus ◽  
Claus Hellerbrand ◽  
Anja K. Bosserhoff ◽  
Peter Dietrich
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
The Future ◽  
Associated Proteins ◽  
Cancer Types ◽  
Novel Therapeutic Strategies

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

scholarly journals An Oncogenic Role for Four-Jointed Box 1 (FJX1) in Nasopharyngeal Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
San Jiun Chai ◽  
Muhammad Mamduh Ahmad Zabidi ◽  
Siew Pey Gan ◽  
Pathmanathan Rajadurai ◽  
Paul Vey Hong Lim ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Southern China ◽  
Metastatic Cancer ◽  
Mrna Levels ◽  
Normal Epithelium ◽  
Tissue Samples ◽  
Exact Function ◽  
Expression Microarrays

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer prevalent in Southern China and Southeast Asia. The current knowledge on the molecular pathogenesis of NPC is still inadequate to improve disease management. Using gene expression microarrays, we have identified the four-jointed box 1 (FJX1) gene to be upregulated in primary NPC tissues relative to nonmalignant tissues. An orthologue of human FJX1, the four-jointed (fj) gene in Drosophila and Fjx1 in mouse, has reported to be associated with cancer progression pathways. However, the exact function of FJX1 in human is not well characterized. The overexpression of FJX1 mRNA was validated in primary NPC tissue samples, and the level of FJX1 protein was significantly higher in a subset of NPC tissues (42%) compared to the normal epithelium, where no expression of FJX1 was observed (p=0.01). FJX1 is also found to be overexpressed in microarray datasets and TCGA datasets of other cancers including head and neck cancer, colorectal, and ovarian cancer. Both siRNA knockdown and overexpression experiments in NPC cell lines showed that FJX1 promotes cell proliferation, anchorage-dependent growth, and cellular invasion. Cyclin D1 and E1 mRNA levels were increased following FJX1 expression indicating that FJX1 enhances proliferation by regulating key proteins governing the cell cycle. Our data suggest that the overexpression of FJX1 contributes to a more aggressive phenotype of NPC cells and further investigations into FJX1 as a potential therapeutic target for NPC are warranted. The evaluation of FJX1 as an immunotherapy target for NPC and other cancers is currently ongoing.

Factors regulating the growth of metastatic cancer in bone.

1999 ◽  
pp. 333-347 ◽  
Author(s):  
B F Boyce ◽  
T Yoneda ◽  
T A Guise
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Bone Cells ◽  
Vascular Endothelial Cells ◽  
Current Knowledge ◽  
Metastatic Cancer ◽  
Bone Matrix ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Surface Proteins

Metastatic tumor cells can interfere directly with the function of bone cells involved in normal bone remodeling or indirectly by influencing the behavior of hematopoietic, stromal and other cells in bone marrow that interact with bone cells. Recent studies of metastatic cancer have revealed that tumor cells interact closely with vascular endothelial cells, basement membrane and bone marrow stromal cells through cell surface proteins or by releasing factors which affect the function of these cells. Bidirectional interaction between marrow cells and tumor cells can give the latter a selective advantage for growth in bone which can lead to the destruction of or to increased production of bone matrix. Understanding of the mechanisms involved in tumor metastasis and growth in bone has increased in recent years, and in this review we shall describe current knowledge of these mechanisms and of the predilection of certain types of cancers to metastasize to bone, their growth in the bone microenvironment and interactions between them and bone cells. Because metastatic breast cancer has been studied more than any other, we shall focus on it as a representative example, although the general principles apply to other types of cancer and to myeloma.

scholarly journals Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 46 ◽  
Author(s):  
Anfray ◽  
Ummarino ◽  
Andón ◽  
Allavena
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Tumor Tissue ◽  
Tumor Response ◽  
Current Knowledge ◽  
Tumor Associated Macrophages ◽  
Cancer Proliferation ◽  
The Past ◽  
Active Research ◽  
Novel Therapeutic Strategies

: Established evidence demonstrates that tumor-infiltrating myeloid cells promote rather than stop-cancer progression. Tumor-associated macrophages (TAMs) are abundantly present at tumor sites, and here they support cancer proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Their pro-tumor activities hamper the response of cancer patients to conventional therapies, such as chemotherapy or radiotherapy, and also to immunotherapies based on checkpoint inhibition. Active research frontlines of the last years have investigated novel therapeutic strategies aimed at depleting TAMs and/or at reprogramming their tumor-promoting effects, with the goal of re-establishing a favorable immunological anti-tumor response within the tumor tissue. In recent years, numerous clinical trials have included pharmacological strategies to target TAMs alone or in combination with other therapies. This review summarizes the past and current knowledge available on experimental tumor models and human clinical studies targeting TAMs for cancer treatment.

scholarly journals From Good to Bad: The Opposing Effects of PTHrP on Tumor Growth, Dormancy, and Metastasis Throughout Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Courtney M. Edwards ◽  
Rachelle W. Johnson
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Patient Survival ◽  
Current Knowledge ◽  
Bone Destruction ◽  
Tumor Dormancy ◽  
Biologically Active ◽  
Improve Patient Survival ◽  
Parathyroid Hormone Related Protein ◽  
Improve Patient

Parathyroid hormone related protein (PTHrP) is a multifaceted protein with several biologically active domains that regulate its many roles in normal physiology and human disease. PTHrP causes humoral hypercalcemia of malignancy (HHM) through its endocrine actions and tumor-induced bone destruction through its paracrine actions. PTHrP has more recently been investigated as a regulator of tumor dormancy owing to its roles in regulating tumor cell proliferation, apoptosis, and survival through autocrine/paracrine and intracrine signaling. Tumor expression of PTHrP in late stages of cancer progression has been shown to promote distant metastasis formation, especially in bone by promoting tumor-induced osteolysis and exit from dormancy. In contrast, PTHrP may protect against further tumor progression and improve patient survival in early disease stages. This review highlights current knowledge from preclinical and clinical studies examining the role of PTHrP in promoting tumor progression as well as skeletal and soft tissue metastasis, especially with regards to the protein as a regulator of tumor dormancy. The discussion will also provide perspectives on PTHrP as a prognostic factor and therapeutic target to inhibit tumor progression, prevent tumor recurrence, and improve patient survival.

scholarly journals Remodeling the ECM: Implications for Metastasis and Tumor Dormancy

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4916
Author(s):  
Julie S. Di Martino ◽  
Tasmiah Akhter ◽  
Jose Javier Bravo-Cordero
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Disseminated Tumor Cells ◽  
Tumor Dormancy ◽  
Primary Tumors ◽  
Ecm Remodeling ◽  
The Individual

While most primary tumors can be effectively treated, therapeutics fail to efficiently eliminate metastases. Metastases arise from cancer cells that leave the primary tumor and seed distant sites. Recent studies have shown that cancer cells disseminate early during tumor progression and can remain dormant for years before they resume growth. In these metastatic organs, cancer cells reside in microenvironments where they interact with other cells, but also with the extracellular matrix (ECM). The ECM was long considered to be an inert, non-cellular component of tissues, providing their architecture. However, in recent years, a growing body of evidence has shown that the ECM is a key driver of cancer progression, and it can exert effects on tumor cells, regulating their metastatic fate. ECM remodeling and degradation is required for the early steps of the metastatic cascade: invasion, tumor intravasation, and extravasation. Similarly, ECM molecules have been shown to be important for metastatic outgrowth. However, the role of ECM molecules on tumor dormancy and their contribution to the dormancy-supportive niches is not well understood. In this perspective article, we will summarize the current knowledge of ECM and its role in tumor metastasis and dormancy. We will discuss how a better understanding of the individual components of the ECM niche and their roles mediating the dormant state of disseminated tumor cells (DTCs) will advance the development of new therapies to target dormant cells and prevent metastasis outgrowth.

scholarly journals Molecular and Metabolic Reprogramming: Pulling the Strings Toward Tumor Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ana Hipólito ◽  
Filipa Martins ◽  
Cindy Mendes ◽  
Filipa Lopes-Coelho ◽  
Jacinta Serpa
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Great Majority ◽  
Tumor Formation ◽  
Metabolic Reprogramming ◽  
Efficient Treatment ◽  
Secondary Tumors ◽  
Metastatic Cells ◽  
Multistep Process

Metastasis is a major hurdle to the efficient treatment of cancer, accounting for the great majority of cancer-related deaths. Although several studies have disclosed the detailed mechanisms underlying primary tumor formation, the emergence of metastatic disease remains poorly understood. This multistep process encompasses the dissemination of cancer cells to distant organs, followed by their adaptation to foreign microenvironments and establishment in secondary tumors. During the last decades, it was discovered that these events may be favored by particular metabolic patterns, which are dependent on reprogrammed signaling pathways in cancer cells while they acquire metastatic traits. In this review, we present current knowledge of molecular mechanisms that coordinate the crosstalk between metastatic signaling and cellular metabolism. The recent findings involving the contribution of crucial metabolic pathways involved in the bioenergetics and biosynthesis control in metastatic cells are summarized. Finally, we highlight new promising metabolism-based therapeutic strategies as a putative way of impairing metastasis.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

Sign in / Sign up

Export Citation Format

Share Document