> For the complete documentation index, see [llms.txt](https://myhealingcommunity.gitbook.io/myhealingcommunity-docs/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://myhealingcommunity.gitbook.io/myhealingcommunity-docs/bone-metastases/dormant-cancer-cells-in-bone-what-this-2025-review-reveals.md). # Dormant cancer cells in bone: what this 2025 review reveals In 2025, Bakir and colleagues published a detailed review on how dormant cancer cells in bone “wake up” and turn into active metastases, especially in breast, prostate, and lung cancer.\ \ **Microenvironmental and Molecular Pathways Driving Dormancy Escape in Bone Metastases.**\ [**https://www.mdpi.com/1422-0067/26/24/11893**](https://www.mdpi.com/1422-0067/26/24/11893) The paper pulls together a large body of work showing that bone is not just a passive site where cells land. It is an active ecosystem that can either keep disseminated tumour cells asleep for years or provide the signals that push them back into growth. They describe how bone-forming cells (osteoblasts), bone-resorbing cells (osteoclasts), bone marrow fat cells, blood vessels, immune cells and even the nervous system all influence whether cancer cells stay in a quiet, non-dividing state or re-enter the cell cycle. In simple terms, the “sleep-supporting” environment is one where osteoblasts are healthy, bone turnover is controlled, immune surveillance is intact, inflammation is low-grade, and the micro-environment is mechanically and metabolically stable. In contrast, excessive osteoclast activity, chronic inflammation, marrow fat dysregulation, immune suppression, and chronic stress signals tend to push cells toward reactivation. One of the strengths of this review is that it doesn’t focus on a single pathway. It shows how osteoclast activation, bone resorption, adipokines, neutrophil extracellular traps, angiogenesis, epigenetic changes and metabolic shifts all converge on a common outcome: switching dormant cells from a p38-high/ERK-low, quiescent profile into an ERK-high, proliferative state. It also makes clear that dormancy is not just a tumour-intrinsic programme. It is co-created by the niche, which means there are multiple potential intervention points. At the same time, the review is quite conservative about translation. Most of the mechanistic insights come from preclinical models, and the authors are careful to acknowledge that we still lack definitive human data showing that manipulating these pathways in a targeted way will reliably prevent late bone relapse. They highlight anti-resorptive drugs such as bisphosphonates and denosumab, along with immune-modulating approaches, as the most clinically advanced strategies. They also note that epigenetic and metabolic interventions remain promising but context-dependent and are not yet ready as dormancy-specific tools. For patients and advocates, this review is valuable because it validates a systems view. Bone health, metabolic health, inflammation, immune tone, stress and treatment timing all matter for the bone dormancy story. Many of the levers we can act on are indirect, and they sit alongside, not instead of, evidence-based cancer treatment. In the sections that follow, the practical takeaways are grouped into **Core levers** and **Supporting levers**. ### Core levers (highest-impact, broadly applicable) These are the things most likely to make a meaningful difference to the “bone dormancy” environment and overall outcomes, and they usually align with standard care. #### 1. Bone-protective medical care * Work with your oncology team to decide if or when bone-active drugs are appropriate, including bisphosphonates or denosumab, especially with endocrine therapy or higher relapse risk. * Arrange regular bone density scans and manage osteopenia or osteoporosis proactively rather than reactively. * Review bone health together with hormone status, including menopause, aromatase inhibitors, or androgen deprivation where relevant. #### 2. Movement that loads bone and preserves muscle * Build in regular weight-bearing and resistance exercise, tailored to safety and fracture risk. * Avoid prolonged immobilisation and use physio or rehab support after surgery or during treatment to stay as mobile as is safely possible. #### 3. Bone-relevant nutrition and micronutrient sufficiency * Ensure adequate calcium, vitamin D3 and K2, magnesium, zinc, boron, silicone, and protein intake through food and or supplements as advised. * Aim for a generally nutrient-dense pattern rather than an ultra-restrictive one, so bone and immune cells have what they need. #### 4. Metabolic health and insulin sensitivity * Use a whole-food, low-GI-leaning pattern that is fibre-rich and minimally processed to support glucose control. * Combine this with regular physical activity and solid sleep to reduce visceral fat and improve insulin sensitivity. * Where lifestyle alone is not enough, use glucose-, blood-pressure-, and lipid-lowering medications appropriately with your team. #### 5. Inflammation and immune tone * Identify and treat chronic infections or inflammatory and autoimmune conditions with your clinicians. * Shift toward an anti-inflammatory eating pattern built around plants, fibre, and quality fats, with less ultra-processed food, sugar, and trans fats. * Protect sleep and circadian rhythm, since these are central for T-cell and NK-cell function. #### 6. Smoking, alcohol, and foundational lifestyle * Stop smoking, or get structured support to do so. * Keep alcohol within guidelines or avoid it where recommended. * Maintain some daily movement plus two to three structured exercise sessions a week if possible. *** ### Supporting levers (helpful refinements on top of the core) These are helpful additions that may further improve the bone and systemic environment, especially once the core levers are in place. #### 1. Stress, sympathetic tone, and nervous system regulation * Embed regular stress-reduction practices such as breathwork, mindfulness, yoga, time in nature, therapy, or peer support. * Prioritise sleep hygiene and a steady day-night rhythm to calm chronic sympathetic activation. * Be mindful with stimulants and avoid leaning on high caffeine or other stimulants to push through ongoing stress. #### 2. Detailed cardiometabolic and vascular support * Keep an eye on blood pressure, lipids, and glucose, and work with your team to tune medication and lifestyle so these stay well controlled. * Use regular movement and diet quality to support endothelial health and a more stable microvasculature. #### 3. Marrow fat and adipokines via body composition work * Focus on gradual, sustainable improvements in body composition, especially reducing central or visceral fat. * Combine nutrition, strength training, and aerobic activity rather than chasing rapid weight loss or single-lever fixes. * Avoid extreme crash dieting or unsupervised prolonged fasting during or after treatment. #### 4. Mechanics, fascia, and movement quality * Use physiotherapy or exercise physiology support to address biomechanical issues, pain, or post-surgical limitations. * Aim for moderate, regular loading rather than alternating between very little movement and repeated high-impact strain. #### 5. Psychosocial and mental health support * Maintain social connection with family, friends, groups, or online communities as a deliberate part of care. * Seek counselling or psychological support when anxiety, low mood, or trauma responses are persistent. #### 7. Cautious exploration of advanced levers * Discuss metabolic agents such as metformin with your oncology or endocrine team if there is a strong rationale in your case. * Consider epigenetic-targeting drugs or trials only within structured, supervised research settings. * Avoid DIY epigenetic hacking with potent supplements. ### Related pages * [Bone Metastases](/myhealingcommunity-docs/bone-metastases.md) * [Denosumab and Zoledronic Acid](/myhealingcommunity-docs/bone-metastases/denosumab-and-zoledronic-acid.md) * [Endocrine Therapy, Stable Disease, and Dormancy in ER-Positive Breast Cancer](/myhealingcommunity-docs/breast-cancer/er-positive-her2-negative/endocrine-therapy-resistance-and-dormancy/endocrine-therapy-stable-disease-and-dormancy-in-er-positive-breast-cancer.md) --- # Agent Instructions This documentation is published with GitBook. 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