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The NCI-led study began in 2014 when researchers collected case information from super-responders and used a variety of technology platforms to analyze the genomes of their tumors and other cells.
according to NCI's definition, the tumors of these super-responders shrink or disappear completely after receiving specific treatments, which typically have an effect on less than 10 percent of patients in clinical trials.
or these patients had more than three times the duration of remission in a typical patient.
By analyzing patients' DNA mutations, RNA expression levels, changes in the number of DNA copies, changes in DNA methylation status, and analysis of immune cells in tumor micro-environments, the researchers found that in 26 patients, multiple mechanisms could mediate super-responses, including specific gene variants and changes in immune cell behavior.
dna damage repair mechanism disorder Many super-responder tumors carry genetic mutations that lead to the loss of dna damage repair mechanisms in cells, which makes tumor cells particularly sensitive to chemotherapy drugs that damage DNA.
a glioblastoma patient was treated with a DNA methylation agent called temozolomide when the disease returned after surgery, radiotherapy and local chemotherapy.
patient then survived for more than 10 years.
analysis of his tumor genome found that two complementary signaling paths to repair DNA damage were a disordered due to genetic mutations.
Interestingly, another colon cancer patient in the study had a period of nearly four years of remission after receiving a combination of thymosamine and a new drug, and although only one signaling path to repair DNA damage in his tumor was abnormal due to a genetic mutation, the treatment he received successfully inhibited another PATH of DNA injury repair.
that the results suggest that for some patients, using combination therapy to block different DNA repair signaling path paths may be an effective strategy.
in six patients who had a super-response to platinum-containing chemotherapy, the researchers found mutations in the BRCA1, BRCA2, or PALB2 genes.
these genetic mutations have demonstrated the potential of targeted DNA damage repair mechanisms in another way.
mechanisms mediate super-responses, including DNA damage repair pathfours and immune system intervention (Photo source: Reference: Reference) The emergence of specific immune cells in the tumor micro-environment Cancer immunotherapy has become one of the main pillars of cancer treatment.
the study, the researchers also found that the number of immune cells in the tumor micro-environment of multiple super-responders was different from that of the average patient.
the number of B lymphocytes and natural killer cells in the micro-environment of multiple super-responders' tumors increased significantly compared to samples from the Cancer Genome Atlas (TCGA).
that the involvement of the immune system may be one of the reasons for the super-response.
"Our findings demonstrate the importance of molecular biology testing of patient tumors," said study co-author Dr. Louis M. Staudt of NCI. "Molecular biobiological testing of tumors provides us with information that cannot be provided by looking at tissue slices under a microscope."
", a proof-of-concept study, shows that research on super-respondents is not only feasible, but can also help us get as much information from them as possible.
senior author of the study, NCI's S. Dr Percy Ivy added.
, researchers in North America, Europe and Australia are currently working on similar super-responder research projects, and NCI researchers hope to pool the data for analysis.
Staudt hopes to conduct a study of at least 1,000 patients.
"There are still a lot of puzzles waiting to be answered," he said.
" References: 'Exceptional' cancer patients yield clues to better drug treatments. Retrieved November 29, 2020, from [2] Study of "exceptional responders" yields clues to cancer and potential treatments. Retrieved November 29, 2020, from [3] Wheeler et al., (2020). Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment. Cancer Cell,