By Cathy Clark, APR - March 10, 2021
For some patients with breast cancer, bone metastasis can pose more danger than the initial diagnosis. Dr. Marilena Tauro has made it her mission to help stop what is called the vicious cycle of cancer cell growth into the bone.
“One of the problems with some breast cancer patients is that when they arrive in the clinic, their cancer already has metastasized,” said Tauro, a research scientist in Moffitt Cancer Center’s Tumor Biology Department. “And the skeleton is one of the most affected organs, mainly because the bone offers the perfect conditions for the cancer cells to seed and grow — it is truly a fertile soil for cancer.”
Tauro, a chemist and a biologist, is using novel molecules she developed while earning her PhD in pharmaceutical chemistry at the University of Bari, Italy. Much of her current preclinical work at Moffitt is focused on molecules designed to attack breast cancer cells that had escaped the primary tumor site and spread to the bone.
“During my PhD work, I designed and synthesized multiple series of small molecules as inhibitors of different enzymes involved in the tumor microenvironment,” said Tauro. The presence of cancer cells in bone induces a vicious cycle between tumor cell growth and bone resorption.
“In the chemistry lab, I was able to take the backbones of two different molecules and fuse them into one that could be selectively active in the bone, to break the vicious cycle and arrest cancer growth,” she said.
Bone metastasis is serious, with 70% of primary tumors spreading to the bone (spine, pelvis, ribs and long bones). The harsh symptoms can include bone pain, fractures and spinal cord compression. Treatment options for this condition include chemotherapy, radiation therapy, surgery, bisphosphonates (a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases) and pain management.
“We have basically two types of bone cells: osteoblasts, the ones that form the bone, and osteoclasts, the ones that ‘chew’ the bone and are involved with bone resorption. The balance between the two of them gives us the healthy skeleton,” said Tauro. “But when the cancer cells arrive to the bone, they make the osteoclasts produce many enzymes leading to degradation of the bone itself, which gives space for the cancer cells to grow. In the bone tissue are many growth factors and as they get released, they end up becoming the nutrients for cancer cells.” Tauro identified the role of specific enzymes, called matrix metalloproteinases, involved at different steps of the metastatic process. Those enzymes get released from both cancer and bone cells, activating factors that facilitate cancer growth. Ultimately the cancer cells take over the bone and result in the formation of a new tumor.
Tauro and her colleagues are using a well-established model to study the effectiveness of the molecules she developed to help break the cycle with the aim of preventing bone metastasis. The molecules she designed are capable to accumulate only into the bone, avoiding side effects in other organs. Here, they fit into the enzyme and disrupt the cycle.
She works in the laboratory of Dr. Conor Lynch in Tumor Biology and also works with Moffitt’s Drug Discovery Department on drugs being produced at Moffitt and tested as possible clinical trial candidates. With her background in chemistry and biology, Tauro understands the challenges in both fields and is able to help transition a drug from its discovery and bring it to preclinical testing, with the ultimate goal of seeing the science translated into a clinical trial.
“We are living in an exciting time for technologies and science,” said Tauro. “I hope this research opens a new way to design drugs that can stop this vicious cycle mechanism that cancer cells use to grow and spread.”
Tauro considers her vocation to be a mission and clearly is passionate about her research and advocacy work. For the patients who develop breast cancer in their lifetime, her work could be a benefit. Her work is not limited to breast cancer, however, because the study model she uses for stopping the vicious cycle of cancer cells to the bone also is relevant to multiple myeloma and prostate cancer that has spread.
“We are all together in this fight against cancer, and every morning when I wake up, I feel I have to come to work to change even one person’s life,” said Tauro. “When you walk across the clinic wearing your lab coat and patients stop you and talk to you with so much hope in their eyes, you have a moral duty to do as much as you can to make a difference. The research is the cure! We made so much progress in cancer care because of research, but much more must still be done.
“It is super exciting because now we have all the technologies to make incredible discoveries and advance faster in this field. Because this is a continuous fight against time. Nobody can waste time. And it’s an investment. Whatever we are doing today is going to pay off. That’s my biggest motivation.”
When not in the lab, Tauro can be found working as a patient advocate at community outreach events where she tells patients about the importance of basic science in finding cures for cancer. She also is heavily involved with advocacy for research awareness to help prompt funding at the state and national levels.