Targeting The Vicious Cycle Of Cancer-induced Bone Disease With TRAIL And Bisphosphonates
Funder
National Health and Medical Research Council
Funding Amount
$443,696.00
Summary
The most serious clinical problem with patients with many forms of solid tumours is metastasis to bone, which leads to potentially debilitating complications that can cause erosion of the patient's quality of life, and eventually death. Unfortunately, bony metastases usually occur before pre-emptive treatments can be applied to prevent it. We have recently shown that recombinant soluble TRAIL is a potent anticancer agent that prevents cancer-induced bone destruction in a mouse model by directly ....The most serious clinical problem with patients with many forms of solid tumours is metastasis to bone, which leads to potentially debilitating complications that can cause erosion of the patient's quality of life, and eventually death. Unfortunately, bony metastases usually occur before pre-emptive treatments can be applied to prevent it. We have recently shown that recombinant soluble TRAIL is a potent anticancer agent that prevents cancer-induced bone destruction in a mouse model by directly targeting cancer cells within bone, and with no evidence of toxic side effects to normal tissues. Death receptor targeting by TRAIL, and bisphosphonates induce cancer cell apoptosis through different but overlapping signaling pathways. Therefore, combination of the two approaches may facilitate killing of tumour cells that resist death induction through either one of the pathways. Combination therapy may also reduce the probability of acquired resistance to either therapy. We propose that a combinatorial approach, using bisphosphonates to selectively target osteoclasts and TRAIL to selectively target cancer cells, would be an ideal therapeutic and safe approach to delay, slow or completely eliminate growth of cancer within bone.Read moreRead less
Is Bisphosphonate Use For The Treatment Of Benign Bone Disease Associated With Impaired Dental Healing?
Funder
National Health and Medical Research Council
Funding Amount
$238,160.00
Summary
Osteoporosis (OSP) is a common condition where bones are thin and may break (fracture). Currently, approximately 2 million Australians suffer from OSP. This figure will rise over the next 20 years as people age. Recommended drug treatment of OSP involves medication called bisphosphonates. Recent research, including a warning from the National Adverse Drug Reaction Committee, has suggested a possible association between bisphosphonates and bone breakdown in the jaw (osteonecrosis) - a devastating ....Osteoporosis (OSP) is a common condition where bones are thin and may break (fracture). Currently, approximately 2 million Australians suffer from OSP. This figure will rise over the next 20 years as people age. Recommended drug treatment of OSP involves medication called bisphosphonates. Recent research, including a warning from the National Adverse Drug Reaction Committee, has suggested a possible association between bisphosphonates and bone breakdown in the jaw (osteonecrosis) - a devastating condition for which no effective treatment exists. This study seeks to determine if bisphosphonate use for the treatment of OSP or other non-cancerous (benign) bone disease (eg Paget's disease) slows dental healing and increases the risk of jaw osteonecrosis. This has major implications and significant potential benefits for the large numbers of people with OSP taking bisphosphonates. Currently, the chance of dental complications during bisphosphonate therapy and what factors predispose to such complications remains unclear. Given the large numbers of people at risk, these are important issues that require urgent careful investigation. We want to determine if long-term (more than 2 years' duration) bisphosphonate treatment of OSP or other benign bone disease slows dental healing and leads to jaw osteonecrosis. We will use a case-control study design given the expected low likelihood of slowed dental healing. This design involves identifying patients with slowed dental healing (cases), and patients with normal dental healing (controls). Cases and controls will then be compared for bisphosphonate use to see if it is more likely that cases have been taking bisphosphonates. Our results will help guide treatment recommendations for these drugs both nationally and internationally.Read moreRead less