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Last Updated: 08/16/21

Exceptional Responders

The DNA double helix rests on a field of ACGTs and binary numbers.

The DCTD and CDP partnered with NCI’s Center for Cancer Genomics (CCG) in the Exceptional Responders Initiative, which invited clinicians to submit cases and tumors from patients who had an exceptional response to their chemotherapy treatment (targeted or standard chemotherapy).

The study defined an exceptional responder as patients who either:

  • had a partial or complete response to a treatment that would be expected to be effective in less than 10% of similarly treated patients; or,
  • had a response to treatment that lasted at least three times longer than the median response time.

Extensive molecular profiling was performed on tumor specimens from 111 patients identified as exceptional responders. Researchers used multiple approaches to develop hypotheses about the reason for the patient’s exceptional response, including analysis of:

  • DNA mutations
  • RNA expression levels
  • DNA copy number alterations
  • DNA methylation
  • Immune cells in the tumor microenvironment

For almost a quarter of patients in the study (23.4%), researchers were able to identify molecular mechanisms that could potentially explain the exceptional responses to treatment. The results demonstrate the importance of testing patient tumors for genetic alterations that may signal uncommon or long-lasting responses to treatment.

More research and additional analytical approaches are needed to describe the molecular underpinnings of the unsolved cases of exceptional responders. NCI and partners on this project have made the molecular profiling results and clinical information publicly available in the NCI Genomic Data Commons to encourage further research and investigation into exceptional responders.

See the following recent publication on exceptional responders:

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. 2021 Jan 11;39(1):38-53.e7. doi: 10.1016/j.ccell.2020.10.015. Epub 2020 Nov 19. PMID: 33217343.