Print This Page
Understanding Cancer Biology to Improve Responses to Therapies
Cancers can outsmart various therapies by becoming more resistant to cell death and, in turn, becoming more aggressive.
Scott I. Abrams, Ph.D., (pictured) Associate Professor of Oncology in the Department of Immunology at Roswell Park Cancer Institute, notes, “The Holy Grail of effective cancer treatment is to better understand cancer biology and identify key changes in cancer cells that modulate their sensitivity to cell death.”
Although cancer cell death is frequently defined in the context of chemotherapy or radiotherapy, Dr. Abrams and other investigators at Roswell Park are also studying an experimental therapy called immunotherapy. However, for all cancer therapies, including immunotherapy to work more effectively, cancer cells must express all the machinery to undergo death.
The immunologist has studied IRF-8, short for interferon regulatory factor-8, a signaling protein originally discovered in certain cells of the immune system, which plays an important role in cell function and death. However, his earlier research identified that IRF-8 can also be expressed in certain solid cancer cell models, such as human colon cancer, as well as mouse mammary cancer and mouse sarcoma (cancers of connective tissue, such as bone and muscle). His findings revealed a direct relationship between IRF-8 levels in such cancer cells and their sensitivity to certain forms of immune-mediated cell death.
He says, “When our lab began to better understand the molecular basis for resistance of cancer cells to certain forms of immune-mediated cell death, we identified that IRF-8 levels played an important role. That is, when IRF-8 levels were low, sensitivity to death decreased. If IRF-8 levels were high, sensitivity to death was increased.” Subsequent experiments in his lab established a causal link between IRF-8 levels and the death response in certain cancer cell models.
Now, funded with a $78,869 grant from the Roswell Park Alliance Foundation, Abrams and colleagues are seeking to better understand how IRF-8 is regulated in these cancer models. His early findings in the lab suggest that IRF-8 levels can be boosted and the response to death increased using certain classes of drugs already being tested in cancer patients for other reasons. He then plans to extend this knowledge to mice bearing tumors to study the effects of combining immunotherapy with such agents to further reduce cancer growth. He notes that this approach is akin to a “one-two punch”.
“If it turns out we can better understand what makes certain cancer cells more death-resistant, we can then develop strategies to overcome those defects so that current or new therapies would work better. This project is dedicated to mouse models with the goal that it would provide a pre-clinical set of data to then support extending this concept to the analysis of patients in cancer clinical trials.
Scott I. Abrams, Ph.D., (pictured) Associate Professor of Oncology in the Department of Immunology at Roswell Park Cancer Institute, notes, “The Holy Grail of effective cancer treatment is to better understand cancer biology and identify key changes in cancer cells that modulate their sensitivity to cell death.” Although cancer cell death is frequently defined in the context of chemotherapy or radiotherapy, Dr. Abrams and other investigators at Roswell Park are also studying an experimental therapy called immunotherapy. However, for all cancer therapies, including immunotherapy to work more effectively, cancer cells must express all the machinery to undergo death.
The immunologist has studied IRF-8, short for interferon regulatory factor-8, a signaling protein originally discovered in certain cells of the immune system, which plays an important role in cell function and death. However, his earlier research identified that IRF-8 can also be expressed in certain solid cancer cell models, such as human colon cancer, as well as mouse mammary cancer and mouse sarcoma (cancers of connective tissue, such as bone and muscle). His findings revealed a direct relationship between IRF-8 levels in such cancer cells and their sensitivity to certain forms of immune-mediated cell death.
He says, “When our lab began to better understand the molecular basis for resistance of cancer cells to certain forms of immune-mediated cell death, we identified that IRF-8 levels played an important role. That is, when IRF-8 levels were low, sensitivity to death decreased. If IRF-8 levels were high, sensitivity to death was increased.” Subsequent experiments in his lab established a causal link between IRF-8 levels and the death response in certain cancer cell models.
Now, funded with a $78,869 grant from the Roswell Park Alliance Foundation, Abrams and colleagues are seeking to better understand how IRF-8 is regulated in these cancer models. His early findings in the lab suggest that IRF-8 levels can be boosted and the response to death increased using certain classes of drugs already being tested in cancer patients for other reasons. He then plans to extend this knowledge to mice bearing tumors to study the effects of combining immunotherapy with such agents to further reduce cancer growth. He notes that this approach is akin to a “one-two punch”.
“If it turns out we can better understand what makes certain cancer cells more death-resistant, we can then develop strategies to overcome those defects so that current or new therapies would work better. This project is dedicated to mouse models with the goal that it would provide a pre-clinical set of data to then support extending this concept to the analysis of patients in cancer clinical trials.
