Ecology and evolution of dormant metastasis

Blasco, Maria; Espuny, Irene; Gomis, Roger R.

doi:10.1016/j.trecan.2022.03.002

Cited by 28 publications

(14 citation statements)

References 125 publications

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“…[65] CTCs that survive in secondary organs (i.e., DTCs) can remain in the bone marrow for years, with only approximately 50% of patients presenting with overt metastasis [Figure 1]. [66] Analysis of tumor-infiltrating immune cells in matched primary and metastatic foci, from patients with NSCLC, demonstrated a more immune tolerogenic TME with a lower level of CTLs in the secondary organs, e.g., lungs, brain, liver, distant lymph nodes, kidneys, and bones. [4] To activate a robust immunosupportive TME against cancer metastasis, it is critical to deliver sufficient immunostimulatory components, such as antigen-presenting cells (APCs), into desired regions, e.g., lymph nodes.…”

Section: Nanomedicine-based Strategy For Hijacking Circulation Cellsmentioning

confidence: 99%

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

Zhu

Gao

et al. 2023

Chinese Medical Journal

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As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.

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Section: Nanomedicine-based Strategy For Hijacking Circulation Cellsmentioning

confidence: 99%

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

Zhu

Gao

et al. 2023

Chinese Medical Journal

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“…To date, the most promising biomarker for patient selection is MAF (mesenchymal aponeurotic fibrosarcoma gene), an AP-1 family transcription factor that is amplified in around 20% of primary breast tumours. MAF is a transcription factor that controls many genes, including CD36 and PTHrP, and regulates a diverse range of metastasis-related cellular processes, including initiation of metastasis, adhesion to bone marrow-derived cells and metabolic rewiring, as well as osteoclast differentiation, suggesting that MAF may play a key role in metastasis, especially to bone [ 24 ].…”

Section: Clinical Application and Treatment Guidelinesmentioning

confidence: 99%

Bone-Targeted Agents and Metastasis Prevention

Coleman

2022

Cancers

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The use of bone-targeted treatments has transformed the clinical care of many patients with metastatic breast cancer. In addition, due to the profound effects of bisphosphonates and denosumab on bone physiology and the bone microenvironment, the potential of bone-targeted agents to modify the process of metastasis has been studied extensively. Many adjuvant trials with bisphosphonates in early breast cancer have been performed. Variable outcomes in terms of disease recurrence have been reported, with any treatment benefits apparently influenced by the age and menopausal status of the patients. The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) conducted a meta-analysis of individual patient data from all available randomised trials to investigate this observation further. This meta-analysis failed to show any benefits of adjuvant bisphosphonates in premenopausal women, but highly significant improvements in bone recurrence (RR = 0.72; 95%CI 0.60–0.86, 2p = 0.0002) and breast cancer mortality (RR = 0.82; 95%CI 0.73–0.93, 2p = 0.002) were seen in the 11,767 postmenopausal women included in the meta-analysis. As a result, clinical guidelines recommend the incorporation of adjuvant bisphosphonates that inhibit osteoclast activity into routine clinical care. Denosumab, which has similar effects on bone cell physiology, appears not to consistently influence disease outcomes, perhaps suggesting that it is the “off target” effects of bisphosphonates on immune function and the biological processes involved in metastasis that are important. Predictive biomarkers beyond menopause are being sought and assessment of the transcription factor MAF (mesenchymal aponeurotic fibrosarcoma gene) appears to identify patients able to benefit from the addition of a bisphosphonate to standard adjuvant anticancer therapies.

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“…The endosteal niche, including osteoblasts and osteoclasts, has been reported to provide tumor cells with an environment supporting their survival and outgrowth, however, the role of osteocytes has been rarely addressed ( Zhang et al, 2019 ). Tumor cell dormancy is defined as an arrest in the cell cycle ( Blasco et al, 2022 ; Phan and Croucher, 2020 ). The details of niches and signals that support tumor cell dormancy in bone metastasis are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Mechanically stimulated osteocytes maintain tumor dormancy in bone metastasis of non-small cell lung cancer by releasing small extracellular vesicles

Xie,

Xu,

Liu

et al. 2024

eLife

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Although preclinical and clinical studies have shown that exercise can inhibit bone metastasis progression, the mechanism remains poorly understood. Here, we found that non-small cell lung cancer (NSCLC) cells adjacent to bone tissue had a much lower proliferative capacity than the surrounding tumor cells. Subsequently, it was demonstrated that osteocytes, sensing mechanical stimulation generated by exercise, inhibit NSCLC cell proliferation and sustain the dormancy thereof by releasing small extracellular vesicles with tumor suppressor micro RNAs, such as miR-99b-3p. Furthermore, mechanical loading of the tibia inhibited the bone metastasis progression of NSCLC. Notably, bone metastasis progression of NSCLC was inhibited by moderate exercise, and combinations with zoledronic acid had additive effects. Moreover, exercise preconditioning effectively suppressed bone metastasis progression. This study significantly advances the understanding of the mechanism underlying exercise-afforded protection against bone metastasis progression.

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Ecology and evolution of dormant metastasis

Cited by 28 publications

References 125 publications

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

Bone-Targeted Agents and Metastasis Prevention

Mechanically stimulated osteocytes maintain tumor dormancy in bone metastasis of non-small cell lung cancer by releasing small extracellular vesicles

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