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Cancers
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Invasion and Progression of Solid Tumors in Bone
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Invasion and Progression of Solid Tumors in Bone

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 8893

Special Issue Editor

Dr. Luís Costa

E-Mail Website
Guest Editor
1. Director of Oncology Department of Hospital de Santa Maria, Lisbon, Portugal
2. Associate Professor of Medicine, Oncology & Oncobiology, Lisbon School of Medicine (FMUL) −University of Lisbon, Lisbon, Portugal
Interests: metastases; tumor progression; resistance to therapy; genomic alterations in cancer cells

Special Issue Information

Dear Colleagues,

Invasion and progression of solid tumors in bone is a common phenomenon in cancer and the main cause of metastatic disease in breast and prostate cancer, the two most frequent cancers in western world. Bone metastases are often present in several other solid tumors, such as lung and kidney.

Osteoclast activity stimulation by cancer cells is a key process in bone metastasis development and has become the most attractive hypothesis to explain bone fragility and test new pharmacological treatment approaches for bone metastases.

In fact, when cancer cells become clinically detectable in bone, uncontrolled bone resorption and tumor growth frequently lead to skeletal morbidity, with patients often experiencing bone complications, also termed skeletal-related events (SREs). Bisphosphonates were the first-in-class bone-targeted treatments to change the natural history of solid tumors with bone metastases and reduce the incidence of SREs. Targeting RANKL with Denosumab has been shown to achieve almost complete osteoclast inhibition in bone metastatic disease and is also effective in preventing SREs.

A comprehensive medical approach to the effects of solid tumor invasion and progression in bone currently includes adequate pain management and selection of anticancer drugs in combination with bone-targeted treatments, as part of a multidisciplinary strategy also comprising radiotherapy and surgery whenever indicated. Additionally, the use of bisphosphonates is legitimate in breast cancer to prevent cancer cell invasion and progression in bone.

Bone metastases have provided the first evidence that the scientific dissection of the tumor microenvironment could enable the development of new, not cancer-directed treatment approaches with an impact on the natural history of the disease.

The current Special Issue asks for contributions that provide new insights into the ability of cancer cells to invade bone and on new tools to improve the clinical approach to patients with or at risk of bone metastases.

Dr. Luís Costa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bone metastasis pathophysiology
  • bone metastasis prevention
  • bone pain
  • bone metastasis research
  • bone-targeted agents
  • radiotherapy and radioisotopes to bone metastases
  • skeletal-related events

Published Papers (4 papers)

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Research

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14 pages, 7187 KiB  
Article
Quantitative Assessment of Treatment Response in Metastatic Breast Cancer Patients by SPECT-CT Bone Imaging—Getting Closer to PET-CT
by Mirela Gherghe, Mario-Demian Mutuleanu, Adina Elena Stanciu, Ionela Irimescu, Alexandra Maria Lazar, Radu Valeriu Toma, Oana Gabriela Trifanescu and Rodica Maricela Anghel
Cancers 2023, 15(3), 696; https://doi.org/10.3390/cancers15030696 - 23 Jan 2023
Cited by 4 | Viewed by 2318
Abstract
Background: Cancer represents the major cause of death mainly through its ability to spread to other organs, highlighting the importance of metastatic disease diagnosis and accurate follow up for treatment management purposes. Although until recently the main method for imaging interpretation was represented [...] Read more.
Background: Cancer represents the major cause of death mainly through its ability to spread to other organs, highlighting the importance of metastatic disease diagnosis and accurate follow up for treatment management purposes. Although until recently the main method for imaging interpretation was represented by qualitative methods, quantitative analysis of SPECT-CT data represents a viable, objective option. Methods: Seventy-five breast cancer patients presenting metastatic bone disease underwent at least two Bone SPECT-CT studies using [99mTc]-HDP between November 2019 to October 2022. Results: Our findings show a good positive relationship between the qualitative methods of imaging interpretation and quantitative analysis, with a correlation coefficient of 0.608 between qualitative whole body scintigraphy and quantitative SPECT-CT, and a correlation coefficient of 0.711 between the qualitative and quantitative interpretation of SPECT-CT data; nevertheless, there is a need for accurate, objective and reproducible methods for imaging interpretation, especially for research purposes. Conclusions: Quantitative evaluation of the SPECT-CT data has the potential to be the first choice of imaging interpretation for patient follow up and treatment response evaluation, especially for research purposes, because of its objectivity and expression of uptake changes in absolute units. Full article
(This article belongs to the Special Issue Invasion and Progression of Solid Tumors in Bone)
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13 pages, 284 KiB  
Article
Doxycycline-Induced Changes in Circulating MMP or TIMP2 Levels Are Not Associated with Skeletal-Related Event-Free or Overall Survival in Patients with Bone Metastases from Breast Cancer
by Huijun Zhao, Gregory Pond, Demetrios Simos, Zhou Wang, Susan Robertson, Gurmit Singh, Lisa Vandermeer, Mark Clemons and Christina Lynn Addison
Cancers 2023, 15(3), 571; https://doi.org/10.3390/cancers15030571 - 17 Jan 2023
Cited by 1 | Viewed by 1577
Abstract
Doxycycline is often used as a promoter of inducible gene expression in preclinical models; however, it can also have direct effects on tumor growth and survival. This is due in part to its ability to inhibit cell invasion and regulate matrix metalloproteinase (MMP) [...] Read more.
Doxycycline is often used as a promoter of inducible gene expression in preclinical models; however, it can also have direct effects on tumor growth and survival. This is due in part to its ability to inhibit cell invasion and regulate matrix metalloproteinase (MMP) expression. Given that doxycycline is also osteotropic, a clinical study to assess its effects on modulation of tumor progression or prevention of skeletal-related events (SRE) in patients with bone metastases from breast cancer (the Achilles trial) was undertaken. Patients received 100 mg of oral doxycycline twice daily for 12 weeks, with serum obtained at baseline and 4, 8 and 12 weeks post-initiation of doxycycline treatment. Exploratory analysis of the effects of doxycycline on circulating levels of MMP or tissue inhibitor of matrix metalloproteinase 2 (TIMP2) was performed in enrolled patients. Statistically significant associations were observed between MMP2, MMP9 and TIMP2 at baseline with significant associations maintained between absolute levels and changes in levels of MMP2 and TIMP2 at weeks 4–12 post initiation of doxycycline. Treatment with doxycycline generally resulted in decreases in MMP2 and MMP9 levels with concurrent upregulation of TIMP2 at 12 weeks post-initiation of doxycycline treatment. Despite this, we observed no association with the levels of any of these factors with either SRE-free or overall survival in this patient cohort. In summary, despite observing hypothesized effects of doxycycline administration on surrogate markers of its anti-tumor activity, measures of circulating levels of these biomarkers were not prognostic in this patient population. Full article
(This article belongs to the Special Issue Invasion and Progression of Solid Tumors in Bone)

Review

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9 pages, 1301 KiB  
Review
Bone-Targeted Agents and Metastasis Prevention
by Robert Coleman
Cancers 2022, 14(15), 3640; https://doi.org/10.3390/cancers14153640 - 26 Jul 2022
Cited by 6 | Viewed by 2161
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Invasion and Progression of Solid Tumors in Bone)
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19 pages, 2415 KiB  
Review
A Tailored Approach for Appendicular Impending and Pathologic Fractures in Solid Cancer Metastases
by Joaquim Soares do Brito, Raquel Lopes-Brás, André Abrunhosa-Branquinho, Isabel Fernandes, Inês Gomes, Sandra Casimiro and Luís Costa
Cancers 2022, 14(4), 893; https://doi.org/10.3390/cancers14040893 - 11 Feb 2022
Cited by 2 | Viewed by 2291
Abstract
Advances in medical and surgical treatment have played a major role in increasing the survival rates of cancer patients with metastatic bone disease. The clinical course of patients with bone metastases is often impaired by bone complications, such as bone fractures, which have [...] Read more.
Advances in medical and surgical treatment have played a major role in increasing the survival rates of cancer patients with metastatic bone disease. The clinical course of patients with bone metastases is often impaired by bone complications, such as bone fractures, which have a substantial negative impact on clinical outcomes. To optimize clinical results and prevent a detrimental impact on patients’ health, a tailored approach should be defined for any given patient. The optimal management of impending or pathologic fractures is unknown and relies on a multidisciplinary approach to tailor clinical decisions to each individual patient. The ability to control systemic disease, the extent, location and nature of bone metastases, and the biology of the underlying tumor, are the main factors that will define the strategy to follow. The present review covers the most recent data regarding impending and pathologic fractures in patients with bone metastases, and discusses the medical and surgical management of patients presenting with metastatic bone disease in different clinical settings. Full article
(This article belongs to the Special Issue Invasion and Progression of Solid Tumors in Bone)
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