Treating bone cancer: the potential of an innovative, injectable drug delivery system
In this interview, Lucas Souza, Research Manager at the Royal Orthopaedic Hospital (Birmingham, UK) and Richard Martin, Director of the Aston Advanced Materials Research Centre and Associate Dean for Research at Aston University (Birmingham, UK), discuss the current treatment options and challenges for primary and metastatic bone cancer. Souza and Martin also highlight how the injectable paste, that the hospital and university are working on in collaboration, functions as a drug delivery system and how it can be used to improve treatment and quality of life outcomes in bone cancer patients.
Can you explain the current treatment options for primary and metastatic bone cancer patients?
Bone tumors are either primary, arising from the substance of bone, or metastatic, with tumors originating elsewhere and migrating into bones. The initial treatment of primary bone tumors is with neoadjuvant chemotherapy followed by excision surgery associated with bespoke orthopedic implants and further adjuvant immunotherapy. Unfortunately, advances in treatment of primary bone tumors have reached a plateau over the past 40 years and the 5-year survival rate is approximately 60%.
The migration and attachment of tumor cells to bone result in bone metastasis, which disrupts the local balance between bone formation and resorption and leads to the development of bone lesions, which commonly result in skeletal-related events (SRE) such as fractures and compression of the spinal cord, spinal nerves, major blood vessels and other organs. The presence of metastases is a hallmark of an advanced stage of disease, usually indicating very poor prognosis. Therefore, treatment usually focuses on pain relief and improving functionality. Recent research investigations have demonstrated that the management of metastasis, especially using minimally invasive intralesional interventions, seems to aid in extending a patient’s life expectancy by preventing SREs and maintaining functional levels.
What complexities and challenges come with treating bone cancer?
The most common complications following surgical treatment in bone tumor patients are implant failure, infection and tumor re-occurrence. Re-occurrence rates are particularly high in tumors where complete resections and radiotherapy are challenging due to the proximity to the spinal cord or other vital organs. Intra-lesional interventions to control metastatic bone tumors are prevalent, but the associated bone loss remains a challenge. Consequently, an effective biomaterial that eradicates residual tumor cells and delivers osteoregenerative properties is required, particularly at anatomical sites where curative surgery and radiotherapy are challenging.
Can you explain how the injectable paste will function as a drug delivery system?
The paste will be composed of a mixture of a degradable polymer and fine particles of gallium-containing bioactive glass and bisphosphonates. The polymer will offer structural support for the particles, and, upon injection, it will degrade in a controlled manner, resulting in the localized release of the active particles in the area. The particles of gallium-containing bioactive glass will release gallium ions, which can kill cancer cells and bacteria at the site, preventing cancer reoccurrence and bacterial contamination. In addition, the bioactive glass will stimulate faster bone regeneration, and new bone will progressively replace the degrading paste.
Over time, we expect the whole paste to be replaced by natural bone and that this new bone will be rich in bisphosphonates –which have the potential to prevent bone resorption – and consequently prevent the development of bone lesions and bone metastases in the region.
How could the injectable paste improve outcomes for bone cancer patients?
The use of this material will produce a positive impact the overall clinical management of bone tumors by reducing cancer re-occurrence, improving bone regeneration, reducing the use of antibiotics, hospitalization times and the need to review surgeries, consequently shortening the overall recovery times and treatment costs. In addition, the proposed scaffolds will impose no negative effect upon adjuvant chemotherapy. Taken together, these benefits would increase survival rates, functionality and the quality of life of bone cancer patients. Also, this research seeks to investigate the mode of action of gallium and gallium-doped bioactive glasses as well as their combination with bisphosphonates upon bone cancer cells, which will open new lines of investigation for further research projects to develop new therapeutics.
How would you like your research to be translated into shaping bone cancer care?
The minimally invasive biomaterial developed by this research will represent the new generation of materials for reconstructive surgeries and interventional therapy in bone cancer patients with the potential to significantly improve treatment outcomes. I envision this material being particularly used in cases of bone tumors where complete resections are challenging and in tumors that are non-responsive to radiotherapy (e.g., sarcomas).
Additionally, this biomaterial can be combined with emerging minimally invasive ablative techniques, such as radiofrequency ablation and cryoablation, for intra-lesional procedures to control metastatic bone tumors and other malignancies that affect vertebral bodies, such as chordomas. Patients with benign bone tumors such as giant-cell tumor of bone would also benefit since intralesional ablative procedures could be followed by injection of this bioactive/anticancer paste for bone augmentation and prevention of tumor re-occurrence.
Interviewee profiles:
Dr Lucas Souza works as Research Laboratory Manager at the Dubrowsky Regenerative Medicine Laboratory in the Royal Orthopaedic Hospital (ROH; Birmingham, UK), holds an Early Career Fellowship from Orthopaedic Research UK (ORUK) and an honorary contract as Research Associate at Aston University. His academic career includes a Marie Curie fellowship and teaching roles at Aston Medical School, leading to his current position in the ROH where he manages the operations of the Dubrowsky Laboratory and conducts impactful research on bone cancer therapies.
Professor Richard Martin is Director of the Aston Advanced Materials Research Centre and Associate Dean for Research, Aston University. Martin has been designing at testing bioactive glasses for over 20 years. Recently his team have developed multi-functional bioactive glasses for bone cancer therapy. The bioactive glasses dissolve releasing gallium ions which selectively target cancer cells. In addition, the glasses release calcium and phosphorous ions which promotes bone regeneration. The glasses can also be tailored to incorporate antimicrobial ions to prevent surgical site infections.
The opinions expressed in this interview are those of the author and do not necessarily reflect the views of Oncology Central or Taylor & Francis Group.