ET Keller and LWK Chung (eds)
Sringer-Verlag US (2004)
ISBN: 1-4020-77749-1 339 pages, plus index.
Several types of cancer, including breast, prostate and lung, have a propensity to metastasise to bone, causing severe morbidity and mortality, for which there are no effective cures. Skeletal complications are also a major problem for haematopoietic malignancies such as multiple myeloma and some lymphomas. In Australia, of the 36,000 people who will die of cancer each year, two-thirds will have skeletal involvement and many will suffer from hypercalcaemia or the debilitating pain caused by spinal cord compression and bone fractures of skeletal disease. Most patients with advanced breast cancer or prostate cancer will experience complications caused by bone metastases. Given that approximately one in ten women will develop breast cancer in their lifetime and a similar number of men will develop prostate cancer, the scale of the problem reveals an urgent need to relieve the suffering of these patients. Current treatments are largely palliative.
The lack of effective therapies stems largely from a lack of understanding of the process of metastasis to bone and is confounded by a paucity of clinically relevant models of bone malignancy. The editors of this book, Doctors Evan Keller and Leland Chung, set out to address these issues by inviting top researchers to write review chapters on their areas of expertise.
Issues that should be covered in a comprehensive review of the topic include the biology of normal bone, the basic biology of metastasis and the interactions between tumour cells and stromal tissues within bone. Molecular events and genes specific to particular types of cancer in bone and potential therapies are also important. Most of these topics are covered in a comprehensive way, with an excellent overview of the process of metastasis to the extent that we understand it today.
Animal models on metastasis to bone are infrequent and imperfect. No transgenic mice that develop spontaneous metastasis to bone yet exist and very few transplantable mouse tumours metastasise spontaneously from their orthotopic site (the mammary gland for breast cancer or the prostate gland for prostate cancer) to bone. For breast cancer, one transplantable model has been reported but for prostate cancer, the few tumour lines that will colonise bone usually form osteolytic lesions rather than the osteoblastic lesions seen in patients. This topic is reviewed well in the book and reveals the difficulty of studying a process using imperfect animal models.
Genes implicated in the process of metastasis to bone, including PTHrP, matrix metalloproteinases, endothelins, type I collagen and MIP-1a are reviewed in detail. Two chapters are dedicated to therapy for bone disease. Bisphosphonates are now widely used in a palliative setting and are the only effective therapy for slowing bone destruction. New treatments, based on inhibiting the RANKL/RANK axis are under development and are mentioned briefly in another chapter. A comprehensive overview of gene therapy for prostate cancer metastasis lists a large number of clinical trials underway, offering hope for effective therapy.
Whilst it is difficult in a book of this size to cover all topics pertinent to bone metastasis, an overview of normal bone biology would have been a valuable addition. This topic is covered in part in the chapter on the contribution of RANK, RANKL and osteoprotegerin to skeletal metastasis, but other aspects on regulation of normal bone are not considered. Also, the major focus of the book is on prostate cancer, possibly reflecting the research interests of the editors.
Overall, this text offers an excellent summary of the state of play of our knowledge of skeletal metastasis, pointing clearly to the difficulties of understanding and treating bone disease.