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Molecular Mechanisms of Bone Metastasis: Which Targets Came from the Bench to the Bedside?

Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteo

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TLN1: an oncogene associated with tumorigenesis and progression.

Talin-1 (TLN1), encoded by the TLN1 gene, is a focal adhesion-related protein capable of binding various proteins in the cytoskeleton. It is also expressed at high levels in many cancers wherein it influences cellular adhesion and the activation of integrins. TLN1 is also capable of promoting tumor cell invasivity, proliferation, and metastatic progression, in addition to being a relevant biomarker and therapeutic target in certain cancers. The present review offers a comprehensive overview of current knowledge regarding TLN1 with respect to its structural properties, functions, and role in tu

Whole-body Computed Tomography Versus Dual Energy X‑ray Absorptiometry for Assessing Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder that leads to heterotopic ossification (HO), resulting in progressive restriction of physical function. In this study, low-dose, whole-body computed tomography (WBCT) and dual energy X-ray absorptiometry (DXA) were evaluated to determine the preferred method for assessing total body burden of HO in patients with FOP. This was a non-interventional, two-part natural history study in patients with FOP (NCT02322255; date of registration: December 2014). In Part A (described here), WBCT and DXA scans were individually ass

Extracellular Vesicles in Bone Metastasis: Key Players in the Tumor Microenvironment and Promising Therapeutic Targets.

Extracellular vesicles (EVs) are lipid membranous vesicles that are released from every type of cell. It has become clear that EVs are involved in a variety of biological phenomena, including cancer progression, and play critical roles in intracellular communication through the horizontal transfer of cellular cargoes such as proteins, DNA fragments, RNAs including mRNA and non-coding RNAs (microRNA, piRNA, and long non-coding RNA) and lipids. The most common cause of death associated with cancer is metastasis. Recent investigations have revealed that EVs are deeply associated with metastasis.

A systematic review and meta-analysis of the efficacy and safety of iguratimod in the treatment of inflammatory arthritis and degenerative arthritis.

OBJECTIVE: To assess the efficacy and safety of iguratimod (IGU) in the treatment of inflammatory arthritis and degenerative arthritis. METHODS: Initially, randomized controlled trials (RCTs) on using IGU in treating inflammatory arthritis and degenerative arthritis were systematically gathered from various databases up to February 2024. Subsequently, two researchers independently screened the literature, extracted data, assessed the risk of bias in included studies, and conducted a meta-analysis using RevMan 5.4 software. RESULTS: Fifty-four RCTs involving three inflammatory arthritis were

The Osteoclast in Bone Metastasis: Player and Target.

Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenome

Biomimetic materials for medical applications.

AbstractRecent advances in biomedical research have facilitated the exploration of biomimetic materials and their potential for diagnosing and treating diseases. This review synthesizes reports of recent research into biomimetic materials and provides a focused analysis of their therapeutic and diagnostic efficacy across multiple physiological systems, including the locomotor, digestive, respiratory, urinary, endocrine, nervous, integumentary, hematopoietic, and circulatory systems. These findings highlight the transformative potential of these materials in the management of systemic diseases.

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… Lee et al [ 34 ] developed a nitric oxide-releasing bioinspired scaffold, where alendronate and bone morphogenetic protein 2 (BMP2) promoted osteogenesis, and zinc oxide (ZO) released nitric oxide (NO) to regulate RANKL/osteoprotegerin ratio and suppress osteoclasts via the NO-cGMP-PKG pathway. …

Hedgehog signaling in cancer stem cells: a focus on hematological cancers.

The stem cell paradigm was first demonstrated in hematopoietic stem cells. Whilst classically it was cytokines and chemokines which were believed to control stem cell fate, more recently it has become apparent that the stem cell niche and highly conserved embryonic pathways play a key role in governing stem cell behavior. One of these pathways, the hedgehog signaling pathway, found in all organisms, is vitally important in embryogenesis, performing the function of patterning through early stages of development, and in adulthood, through the control of somatic stem cell numbers. In addition to

Dissecting the effects of 223Radium on the bone microenvironment.

Radium-223 (223Ra) is a bone-seeking, alpha-particle-emitting radionuclide that is approved for the treatment of patients with metastatic prostate cancer and is currently being tested in clinical trials for primary and metastatic cancers to the bone. 223Ra accumulates in mineralized bone areas with high bone turnover, where its effects are confined within 100 μm of the bone-marrow interface due to the short tissue penetrance of the alpha particles. A recent clinical study has shown a significantly increased fracture rate associated with the administration of 223Ra, mostly in tumor-free bones.

Myeloma Bone Disease: The Osteoblast in the Spotlight.

Lytic bone disease remains a life-altering complication of multiple myeloma, with up to 90% of sufferers experiencing skeletal events at some point in their cancer journey. This tumour-induced bone disease is driven by an upregulation of bone resorption (via increased osteoclast (OC) activity) and a downregulation of bone formation (via reduced osteoblast (OB) activity), leading to phenotypic osteolysis. Treatments are limited, and currently exclusively target OCs. Despite existing bone targeting therapies, patients successfully achieving remission from their cancer can still be left with chro

Связь между окисляющим стрессом, митохондриальной дисфункцией, железным метаболизмом и микроглией в множестве склерозов: обзор нарации.

В последние годы в патогенезе множественного склероза особое внимание уделяется митохондриальным процессам, влияющим на начало заболевания. Окисляющий стресс будет одним из последствий митохондриальной дисфункции, и его воздействие на ткани мозга хорошо описано. Микроглия, как макрофаж мозга, имеет важную функцию в удалении нежелательных метаболитов, а также железа, который является усилителем окислительного стресса. Существуют новшества с точки зрения связи между этими процессами, которые в большей степени перенаправляют исследования на сам процесс нейродегенерации, с тем чтобы больше не дела

Cystatin M/E Ameliorates Multiple Myeloma-Induced Hyper Osteolytic Bone Resorption.

Multiple myeloma (MM) is a malignancy of terminally differentiated B-cells that is localized primarily in the bone marrow (BM) but also can be present in peripheral blood and tissue/organs [...].

Novel Developments in the Treatment of Multiple Myeloma-Associated Bone Disease.

Osteolytic bone disease is present in about 80% of patients with multiple myeloma at the time of diagnosis. Managing bone disease in patients with multiple myeloma is a challenge and requires a multi-faceted treatment approach with medication, surgery, and radiation. The established treatments with intravenous or subcutaneous antiresorptives can cause debilitating adverse events for patients, mainly osteonecrosis of the jaw, which, traditionally, has been difficult to manage. Now, oral surgery is recommended and proven successful in 60-85% of patients. Patients with spinal involvement may bene

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… Does the Addition of Bone Morphogenetic Protein 2 to Platelet-Rich Fibrin Improve Healing After Treatment for Medication-Related Osteonecrosis of the Jaw? J. Oral Maxillofac. Surg. 2017 75 1176 1184 10.1016/j.joms.2016.12.005 28042979 52. Ristow O. Otto S. Geiß C. Kehl V. Berger M. Troeltzsch M. …

RANKL/RANK System-Based Mechanism for Breast Cancer Bone Metastasis and Related Therapeutic Strategies.

Breast cancer remains one of the most life-threatening tumors affecting women. Most patients with advanced breast cancer eventually develop metastatic diseases, which cause significant morbidity and mortality. Approximately two-thirds of patients with advanced breast cancer exhibit osteolytic-type bone metastasis, which seriously reduce the quality of life. Therefore, development of novel therapeutic strategies for treating breast cancer patients with bone metastasis is urgently required. The "seed and soil" theory, which describes the interaction between the circulating breast cancer cells (s

Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis.

As one of the most common metastatic sites, bone has a unique microenvironment for the growth and prosperity of metastatic tumor cells. Bone metastasis is a common complication for tumor patients and accounts for 15-20% of systemic metastasis, which is only secondary to lung and liver metastasis. Cancers prone to bone metastasis include lung, breast, and prostate cancer. Extracellular vesicles (EVs) are lipid membrane vesicles released from different cell types. It is clear that EVs are associated with multiple biological phenomena and are crucial for intracellular communication by transportin

Mediterranean Diet Food Components as Possible Adjuvant Therapies to Counteract Breast and Prostate Cancer Progression to Bone Metastasis.

Bone metastasis is a serious and often lethal complication of particularly frequent carcinomas, such as breast and prostate cancers, which not only reduces survival but also worsens the patients' quality of life. Therefore, it is important to find new and/or additional therapeutic possibilities that can counteract the colonization of bone tissue. High adherence to the Mediterranean diet (MD) is effective in the prevention of cancer and improves cancer patients' health, thus, here, we considered its impact on bone metastasis. We highlighted some molecular events relevant for the development of

The skeleton: an overlooked regulator of systemic glucose metabolism in cancer?

Recent discoveries demonstrated the skeleton's role as an endocrine organ regulating whole-body glucose homeostasis. Glucose metabolism is critical for rapid cell proliferation and tumour growth through increasing glucose uptake and fermentation of glucose to lactate despite being in an aerobic environment. This hypothesis paper discusses emerging evidence on how bones can regulate whole-body glucose homeostasis with potential to impact on tumour growth and proliferation. Moreover, it proposes a clinical link between bone glucose metabolism and prognosis of cancer based on recent clinical tria

Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response.

Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on m

Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for over 90% of all cases. Patients with advanced-stage HCC are referred to systemic treatment. Although some advances in HCC therapy have been made in recent years, the prognosis for patients remains poor due to drug resistance, tumor relapse, and metastasis, implying that overall survival remains a challenge. Many studies have shown that tumor-initiating stem cells, also known as cancer stem cells (CSCs), play essential roles in tumorigenesis, metastasis, and treatment resistance in HCC and that future cancer