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Comment
. 2014 Sep;4(9):988-90.
doi: 10.1158/2159-8290.CD-14-0738.

RADical response puts an exceptional responder in CHKmate: a synthetic lethal curative response to DNA-damaging chemotherapy?

Guang Peng  1 , Scott E Woodman  2 , Gordon B Mills  3
Affiliations
Comment

RADical response puts an exceptional responder in CHKmate: a synthetic lethal curative response to DNA-damaging chemotherapy?

Guang Peng et al. Cancer Discov. 2014 Sep.

Abstract

In this issue of Cancer Discovery, AI-Ahmadie and colleagues identify a somatic mutation in the RAD50 gene as a likely contributing factor to an unusual curative response to systemic combination therapy employing the DNA-damaging agent irinotecan and a checkpoint kinase 1 inhibitor in a patient with recurrent, metastatic small-cell cancer. This study highlights the importance of in-depth analysis of exceptional responders to chemotherapy and targeted therapy in early-phase clinical trials and opens new avenues for developing cancer genome-based combination therapy to improve the efficacy of traditional chemotherapy through synthetically lethal interactions.

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Figures

Figure 1
Figure 1
The impaired function of the MRN complex due to a somatic mutation of Rad50 leads to a synthetic lethality in cancer cells when they are treated with Chk1 inhibitor and DNA-damaging chemotherapy irinotecan.
See this image and copyright information in PMC

Comment on

  • Synthetic lethality in ATM-deficient RAD50-mutant tumors underlies outlier response to cancer therapy.
    Al-Ahmadie H, Iyer G, Hohl M, Asthana S, Inagaki A, Schultz N, Hanrahan AJ, Scott SN, Brannon AR, McDermott GC, Pirun M, Ostrovnaya I, Kim P, Socci ND, Viale A, Schwartz GK, Reuter V, Bochner BH, Rosenberg JE, Bajorin DF, Berger MF, Petrini JH, Solit DB, Taylor BS. Al-Ahmadie H, et al. Cancer Discov. 2014 Sep;4(9):1014-21. doi: 10.1158/2159-8290.CD-14-0380. Epub 2014 Jun 16. Cancer Discov. 2014. PMID: 24934408 Free PMC article.

References

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