Exploiting tumour hypoxia as a therapeutic target for skeletal malignancies
Tumour hypoxia (deprivation of oxygen) is a major cause of treatment failure and poor outcome for a wide variety of malignancies. Within most solid tumours, there are significant areas of hypoxia, which contain cancer cells that are resistant to chemotherapy and radiotherapy. This increases the risk of tumour recurrence and metastasis. However, tumour hypoxia also offers treatment opportunities with the development of drugs that can specifically target hypoxic zones. This project investigates the anti-cancer potential of a new class of Hypoxia Activated Pro-drugs (HAPs), uniquely in the context of treatment of bone cancers. It is important to note that bone marrow is more hypoxic (has less oxygen) compared to other tissues which means metastatic cancer cells are therefore attracted to bone marrow. Bone micro-metastases (which are beginning to form micro blood vessels), are under hypoxic stress (deprived of oxygen). As the tumour grows, it develops hypoxic regions due to inadequate blood flow and oxygen. These factors make bone metastases highly susceptible to therapeutic intervention with HAPs.
What we aim to achieve
Cancer in bone is associated with bone destruction, which is responsible for considerable morbidity and reduced quality of life. Bone destruction is the primary cause of morbidity in patients with primary bone cancer, such as osteosarcoma, Ewing’s sarcoma or multiple myeloma. Bone destruction can lead to bone pain, paralysis due to spinal cord compression, hypercalcemia (elevated blood calcium levels), fractures and the need for extensive orthopaedic surgical intervention. The cost of this morbidity is enormous, especially since these patients often survive for a longer time than patients with visceral (internal organ) metastases. Our research will inform future clinical trials of the potential benefit of HAP drugs in limiting the devastating clinical consequences of bone cancer. This is a realistic possibility, given that these groups of agents are currently in clinical (human) trials.
Our next steps and milestones
This study will provide a high level of information for a comprehensive evaluation of the effect of HAPs on bone cancer development, progression and metastatic spread and will have important implications for the planning of future clinical trials. Importantly, the approach we have taken has the real potential of being rapidly translated into the clinical setting since these groups of agents are currently in clinical trials.
What motivates me
I am motivated by working at the forefront of cancer research and contributing to new knowledge with implications in new and effective cancer therapy. Our goal is to continue towards developing new and cutting-edge therapies to improve the quality of life and longevity of patients with bone cancer.
My message to supporters
We are grateful for their generous support. There is hope. However, this hope is only kept alive by breakthroughs in medical research.