Give a big bear hug welcome to Dr. Andy Livingston, QuadW's 2016 Young Investigator through the Conquer Cancer Foundation. He works at MD Anderson Cancer Center, and because of his big heart for teenagers--a sometimes overlooked population--Dr. Livingston has chosen to focus his work on osteosarcoma. YOU ROCK! So happy to have you as the newest member of our team!
This project focuses on 2 mechanisms of stress response in cancer cells to attempt to predict which patients will respond well to chemotherapy and to potentially enhance responses to current treatment in order to improve patient outcomes.
When cancer cells are exposed to stressors such as chemotherapy, they can undergo a process called autophagy (from Greek auto-, "self" and phagein, "to eat") which allows for the breakdown and recycling of cellular components to maintain energy and assemble new proteins. In many cases, this self-eating serves as a protective mechanism to resist the effects of chemotherapy and may be responsible for the recurrence of cancer, as well as the spread of tumor to distant organs. However, when this cellular cannibalism is driven to the extreme, it can lead to cancer cell death. This dual role has been termed the “autophagy paradox” in cancer. Because autophagy can lead to either cancer cell survival or cell death, it has been challenging to find the best way to target autophagy in order to improve responses to conventional chemotherapy.
The heat-shock family of proteins (HSPs) is part of another protective mechanism for cells when exposed to stressors in their environment. HSPs are produced by cells (both cancer cells and normal cells) in response to exposure to stressful conditions such as lack of nutrition, low oxygen levels, and cancer treatments such as chemotherapy and radiation. HSPs help with refolding and repair of cellular proteins damaged by stress and have similarly been shown to be a mechanism of resistance to chemotherapy in many types of cancer. Recently, we have identified one specific heat-shock protein (HSP27) that appears to predict the role of autophagy in osteosarcoma cells. When exposed to chemotherapy, osteosarcoma cells can either increase or decrease levels of HSP27. When HSP27 is increased, autophagy promotes cell survival, and subsequently leads to decreased sensitivity to chemotherapy. Conversely, when it is decreased, these cancer cells are more sensitive to the effects of chemotherapy.
In this project, we are examining the interaction of HSP27 and autophagy in osteosarcoma cells. In addition, we will test novel treatments to inhibit either autophagy or heat-shock proteins to determine if they can improve the efficacy of chemotherapy. We are also analyzing osteosarcoma patient samples to better understand the relationship between HSPs, autophagy, and response to pre-operative chemotherapy. We hope this work will ultimately lead to new treatment strategies that can be added to current chemotherapy.
