New Avenues to treat Bone Pathologies

Bone is a major site of cancer metastases. Skeletal related events such as pathological fractures occur in a third of these patients requiring surgery and palliative radiation. Photodynamic therapy could add, and compliment available treatments. A pre-clinical murine model with induced bone metastases was used to understand the impact of PDT – a non-surgical, non-ionizing minimally invasive local treatment – on tumor and bone. In this work it has been shown that PDT, in addition to killing tumors, rapidly improves vertebral bone strength, stiffness and architecture. This work has now progressed to a Phase I clinical trial. The results of the PDT study motivated a new avenue to exploit the potential effect of PDT on fracture healing. We used a pre-clinical murine fracture model where preliminary results showed increased bone formation in a critical size defect (> 6 mm) in the PDT treatment groups. Prevention of radiation exposure to healthy bone has been a priority in radiotherapy. Despite current efforts such as intensity modulated radiotherapy (IMRT), complications like osteoradionecrosis (ORN), as in Head & Neck cancers or increase in pathological fractures after radiation of sarcomas remain challenging. The etiology of ORN is not completely understood. Here, pre-clinical studies have not taken into consideration the impact of the immune system in maintaining skeletal health. Further, the models used in preclinical studies have been predominately performed on non-tumor bearing or immunocompromised animals, not leading to reproducible results. A relevant preclinical model for ORN, thus needs to include a realistic representation of both the normal and the diseased milieu, present during radiation delivery and response assessment. The establishment of such tumor model facilitates gaining relevant information regarding how radiation treatment induces changes to healthy bone, benefiting patients. Methods to assess changes to bone pathologies include imaging, biomechanics and histopathology.

BIOGRAPHY

margareteakensDr. Margarete Akens is a Scientist at the Techna Institute and an Assistant Professor at the Department of Surgery and a Faculty member of the Spine Program at the University of Toronto. She received her PhD from the Faculty of Veterinary Medicine at the University in Zurich, Switzerland, in 2002. Her research interests include bone related cancers and bone repair with focus on the development of innovative treatment options. She has extensive experience working with pre-clinical bone cancer models and studying the effect of photodynamic therapy on both cancer cells and bone. Additionally she will lead the emerging Comparative Oncology Program at STTARR. Cancer occurs naturally in animals with a similar frequency as in humans, but due to the shorter life span everything happens faster. This program focuses on collaboration between Veterinarians and Physicians to accelerate the knowledge about cancer biology and clinical care.

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