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December 8, 2020
Understanding “exceptional responders” to cancer treatment
At a Glance
- Researchers identified molecular changes in tumors of patients who are exceptional responders to cancer treatments.
- The findings demonstrate how molecular diagnostics could lead to more personalized treatments for patients with cancer.
Chemotherapy is among the most widely used treatments for cancer. These treatments use drugs to stop the growth of cancer cells. The drugs either kill the cells or stop them from dividing. But patients can respond differently to the same treatments.
Exceptional responders are patients who respond to treatments that are not effective for most other patients. In 2014, NIH’s National Cancer Institute (NCI) started an initiative to understand the molecular underpinnings of the exceptional responses to treatment in these patients.
A research team led by Drs. Percy Ivy and Louis Staudt of NCI analyzed tumor tissue—and normal tissue, when available—from 111 patients enrolled in the initiative. The participants had different types of cancer and all received standard treatments. Results were published on November 19, 2020 in Cancer Cell.
The researchers collected detailed medical histories and samples from the participants. They used multiple genomic approaches to examine the samples. These included analysis of DNA mutations, RNA expression levels, DNA copy number alterations, and DNA methylation. They also analyzed disease-fighting immune cells in the tumors’ microenvironment. The microenvironment includes the cells, molecules, and blood vessels that surround and feed a tumor.
The team was able to identify numerous molecular features that may potentially explain exceptional responses to treatment for 26 of the 111 patients.
The mechanisms underlying the exceptional responses fit into several broad categories. These included the body’s ability to repair DNA damage and the immune system’s response to tumors. Another category included rare combinations of genomic changes that resulted in tumor cell death during treatment.
“The majority of patients in this study had metastatic cancers that are typically difficult to treat, yet some of the patient responses lasted for many years,” says Staudt. “Researchers and the doctors who treat these patients have long been curious about the mechanisms underlying these rare responses to treatment. Using modern genomic tools, we can now start to solve these fascinating puzzles.”
“The knowledge gained from studying exceptional responders can help inform how we take care of patients in the future and will help move us closer to the goal of precision oncology,” Ivy adds.
More research is needed to understand the mechanisms underlying the remaining unsolved cases of exceptional responders.
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References: Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment. Wheeler DA, Takebe N, Hinoue T, Hoadley KA, Cardenas MF, Hamilton AM, Laird PW, Wang L, Johnson A, Dewal N, Miller V, Piñeyro D, Castro de Moura M, Esteller M, Shen H, Zenklusen JC, Tarnuzzer R, McShane LM, Tricoli JV, Williams PM, Lubensky I, O'Sullivan-Coyne G, Kohn EC, Little RF, White J, Malik S, Harris L, Weil C, Chen AP, Karlovich C, Rodgers B, Shankar L, Jacobs P, Nolan T, Hu J, Muzny DM, Doddapaneni H, Korchina V, Gastier-Foster J, Bowen J, Leraas K, Edmondson EF, Doroshow JH, Conley BA, Ivy SP, Staudt LM. Cancer Cell. 2020 Nov 16:S1535-6108(20)30546-8. doi: 10.1016/j.ccell.2020.10.015. Online ahead of print. PMID: 33217343.
Funding: NIH’s National Cancer Institute (NCI).