BONES and Cancer — A Triple Whammy
Bone – one of several components of the musculoskeletal system that provides us with strength and mobility – is negatively impacted by cancer, due to: (1) several primary malignancies, (2) being a common site of metastatic spread, and (3) osteoporosis (decreased bone density) and breakage, as a side effect of some cancer treatments. The Hillman investigators who participate in the monthly meetings and annual retreat of the Pittsburgh Center for Bone and Mineral Research, led by Dr. Deborah Galson, are dedicated to saving lives and limbs, and reducing pain and disability.1. Three Primary Cancers That Affect Bone
Osteosarcomas are the bone cancers that lead to limb amputation in children and young adults. Dr. Kurt Weiss is an orthopedic oncologist who operates on pediatric and adult patients with osteosarcoma, conducts basic research on osteosarcoma, and is a long-term osteosarcoma survivor. His work is funded by the National Institutes of Health (NIH), and he recently received a University of Pittsburgh SEED grant, from Chancellor Gallagher’s Office, to advance the efforts of the Pittsburgh Sarcoma Research Collaborative (PSaRC), with colleagues who study other types of sarcomas. Mr. J. Randall McAuley, an MD-PhD student training under Drs. Peter Lucas and Clayton Wiley, is studying the mechanism by which osteosarcoma spreads from the bone to other organ sites. As the recipient of an individual training grant from the National Cancer Institute (NCI), he was one of the trainees featured in the August 2018 Director’s Message.
Chondrosarcomas are the bone cancers that tend to occur in older adults. Drs. Anette Duensing and Nduka Amankulor have teamed together to target the effects of a gene that was recently found to be mutated in the majority of chondrosarcomas. This is an exciting collaboration within Hillman, as Dr. Duensing is a pathologist whose research focuses on sarcomas (she is also a driving force within PSaRC) and Dr. Amankulor is a neurosurgeon who studies gliomas (the type of brain cancer that recently claimed the life of Senator John McCain), which show mutation of the same gene as in chondrosarcomas.
Multiple Myelomas are malignancies that, like leukemias, are a disorder of white blood cells that are formed in the bone marrow. Unlike leukemias, however, the abnormal white blood cells that accumulate in the bone marrow of patients with multiple myeloma release a substance that promotes the rapid and unopposed breakdown of bone. This leads to bone pain and fractures, most frequently in the arms and legs. Dr. Galson conducts research aimed at preventing the breakdown of bone by multiple myeloma and other diseases.2. Metastasis to Bone
Bone is a common site of metastatic spread, with the majority of Stage IV breast and prostate cancer patients showing metastases in bone. Dr. Shilpa Sant, one of our 2018-2019 Hillman Fellows for Innovative Developmental Cancer Research, recently received funding for an innovative pilot project to determine whether primary breast tumors that include microcalcifications are at increased risk of metastasizing to bone. Dr. Shivendra Singh, another 2018-2019 Hillman Fellow for Innovative Developmental Cancer Research is identifying drugs that can be used for prevention of bone degradation and breakage in breast cancer that has metastasized to bone. Dr. Rebecca Watters, who was one of only five investigators in the U.S. to receive a 2017 Young Investigator Award from METAvivor, is focused on discovering gene mutations in the bone metastases of breast cancer patients. The goal is to identify “actionable” mutations that can be safely targeted with drugs, as part of a precision medicine approach to cancer treatment.
3. Treatment-induced Osteoporosis
Women with breast cancer who are treated with aromatase inhibitors, such as anastrozole, letrozole or exemestane, and men with prostate cancer who are treated with androgen deprivation drugs, such as leuprolide, goserelin, triptorelin, or histrelin, are at increased risk of developing osteoporosis. Completed trials led by Dr. Susan Greenspan, a Geriatric Medicine specialist who directs the UPMC Osteoporosis Prevention and Treatment Center and the Bone Health Program, in collaboration with Hillman investigators have led to improved strategies that are now employed for bone-related complications of cancer treatment.
Since even people who do not have cancer can suffer from the effects of poor bone health, I urge you all to remain physically active, refrain from smoking and excessive alcohol consumption, and ensure that your diet includes a sufficient amount of calcium.
Robert L. Ferris, MD, PhD