Assistant Professor Jungwoo Lee of the Chemical Engineering Department is receiving a one-year, $50,000 grant from the METAvivor 2019 Early Career Investigator Award grant program to support his foundational research for developing better therapeutic strategies to prevent or delay lethal metastasis for breast cancer survivors.
In this grant, titled “Tissue-engineered bone to determine the impact of chemotherapy-induced premature aging in breast tumor metastasis,” Lee and his graduate students Yongkuk Park and Jun-Goo Kwak will study critical cancer biology in bone metastasis to apply an artificial bone marrow tissue.
“We consider this grant is a big milestone. As a bioengineering group, our effort is recognized by both the cancer research and patient community,” says Lee. “I intend to evolve this research to attract a grant from the National Cancer Institute.”
According to Lee, bone metastasis is the leading cause of death from breast cancer. About 6 percent of breast cancer patients are positive with metastasis when they are first diagnosed with cancer.
Lee adds that recent preclinical studies reported that tumor cell dissemination occurs even before a primary tumor is established, suggesting that significantly more patients may carry disseminated tumor cells in their bone marrow when the tumor is first diagnosed. And yet, the current standard of care for cancer survivors who may carry disseminated tumor cells is to wait passively and watch for metastatic tumors to develop.
“Successfully disseminated tumor cells in the bone marrow lie dormant for years and decades,” as Lee reports. “Exact mechanisms by which dormant disseminated tumor cells awake and develop lethal metastasis remain uncertain, but the advanced age [of the patient] is an important risk factor.”
Lee explains that chemotherapy is the standard treatment for stage IV (metastatic) breast cancer patients, but this therapy is known to accelerate aging in patients. “For example,” says Lee, “survivors experience osteoporosis much earlier than an age-matched demographic group. Many investigators believe that therapy-induced bone aging is functionally linked to awakening of disseminated tumor cells.”
However, as Lee notes, the mechanism behind this negative process remains unclear due to intrinsic challenges related to investigating bone metastasis in the context of aging. These challenges include the fact that the inner bone cavity is anatomically difficult to access and bone aging and metastasis are lengthy processes.
As Lee says about his research, “We have developed a tissue-engineered bone model that faithfully replicates surface and subsurface of bone tissue complexity in a controlled and analytical manner. The goal of this proposal is to apply a tissue-engineered bone model developed in our lab to determine functional connections between therapy-induced bone aging and metastatic disease progression.”
Lee concludes that “If successful, our tissue-engineered bone model will allow us to ask experimental questions regarding the impact of cancer therapy in bone aging and associated tumor cell biology.” In addition, Lee’s research could also lead to pioneering therapeutic therapies to impede lethal metastasis.
Lee runs the Lee Research Group, an interdisciplinary lab in the Chemical Engineering Department and the Institute for Applied Life Sciences at the University of Massachusetts Amherst. The mission of his lab is to deliver enabling and translational platform technologies that can advance basic biomedical research, solve various medical problems, and ultimately improve patient care.
“We design and manufacture a broad range of materials to construct standardized, functional human tissue models and apply multi-dimensional imaging modalities to quantitatively capture complex, dynamic biological processes,” says Lee. (February 2020)