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Molecular cancer screening: in search of evidence

Cancer screening with germline genetic sequencing and liquid biopsy could facilitate early cancer detection. But testing if these technologies reduce the burden of cancer mortality will require rethinking how clinical trials are run.

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Fig. 1: Molecular technologies for cancer screening.
Fig. 2: Standard versus adaptive approach to regulation and assessment of novel cancer screening interventions.


  1. The American Cancer Society. (2020).

  2. Plichta, J. K., Griffin, M., Thakuria, J. & Hughes, K. S. Oncology 30, 787–799 (2016).

    PubMed  Google Scholar 

  3. Chen, M. & Zhao, H. Hum. Genomics 13, 34 (2019).

    Article  Google Scholar 

  4. Yurgelun, M. B., Chenevix-Trench, G. & Lippman, S. M. Cell 168, 566–570 (2017).

    CAS  Article  Google Scholar 

  5. Turnbull, C., Sud, A. & Houlston, R. S. Nat. Genet. 50, 1212–1218 (2018).

    CAS  Article  Google Scholar 

  6. Haverfield, E. et al. BMC Med. (in the press).

  7. Manchanda, R., Lieberman, S., Gaba, F., Lahad, A. & Levey-Lahad, E. Annu. Rev. Genomics. Hum. Genet. 21, 373–412 (2020).

    CAS  Article  Google Scholar 

  8. Hall, M. J., Forman, A. D., Pilarski, R., Wiesner, G. & Giri, V. N. J. Natl. Compr. Canc. Netw. 12, 1339–1346 (2014).

    Article  Google Scholar 

  9. De Rubis, G., Krishnan, S. R. & Bebawy, M. Pharmacol. Res. 136, 35–44 (2018).

    Article  Google Scholar 

  10. Lennon, A. M. et al. Science 369, eabb9601 (2020).

    CAS  Article  Google Scholar 

  11. Liu, M. C. et al. Ann. Oncol. 31, 745–759 (2020).

    CAS  Article  Google Scholar 

  12. Heyn, H. & Esteller, M. Nat. Rev. Genet. 13, 679–692 (2012).

    CAS  Article  Google Scholar 

  13. Luo, H. et al. Sci. Transl. Med. 12, eaax7533 (2020).

    CAS  Article  Google Scholar 

  14. Aravanis, A. M., Lee, M. & Klausner, R. D. Cell 168, 571–574 (2017).

    CAS  Article  Google Scholar 

  15. Chen, X. et al. Nat. Commun. 11, 3475 (2020).

    CAS  Article  Google Scholar 

  16. Bradley, S. H. & Barclay, M. E. Br. Med. J. 372, m4933 (2021).

    Article  Google Scholar 

  17. Mathews, S. C. et al. NPJ Digit. Med. 2, 38 (2019).

    Article  Google Scholar 

  18. Johnston, J. L., Dhruva, S. S., Ross, J. S. & Rathi, V. K. Nat. Biotechnol. 38, 933–938 (2020).

    CAS  Article  Google Scholar 

  19. American Society of Clinical Oncology. J. Oncol. Pract. 3, 296–301 (2007).

    Article  Google Scholar 

  20. Reynolds, I. S., Rising, J. P., Coukell, A. J., Paulson, K. H. & Redberg, R. F. JAMA Intern. Med. 174, 1773–1779 (2014).

    Article  Google Scholar 

  21. Resnic, F. S. et al. N. Engl. J. Med. 376, 526–535 (2018).

    Article  Google Scholar 

  22. Wallach, J. D. et al. Br. Med. J. 361, k2031 (2018).

    Article  Google Scholar 

  23. Curran, G. M., Bauer, M., Mittman, B., Pyne, J. M. & Stetler, C. Med. Care 50, 217–226 (2012).

    Article  Google Scholar 

  24. Srivastava, S. et al. Nat. Rev. Cancer 19, 349–358 (2019).

    CAS  Article  Google Scholar 

  25. Rathi, V. K., Krumholz, H. M., Masoudi, F. A. & Ross, J. A. JAMA Netw. Open 3, e2014496 (2020).

    Article  Google Scholar 

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The viewpoints expressed herein are those of the authors and do not reflect official viewpoints of the US National Institutes of Health, The Center for Medicare & Medicaid Innovation, CMS or the companies mentioned. The authors appreciate helpful comments on earlier drafts of this article from S. Aldubayan, H. Hampel, A. Kesselheim and R. Weinberg. R.C.G. is supported by US National Institutes of Health grants HG006500, HD077671, HD090019, HG009922, HL143295 and TR003201 and by the Franca Sozzani Fund.

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Correspondence to Sana Raoof.

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S.R. receives consulting fees from Grail. C.J.K. is an employee of UnitedHealth Group and owns stock in the company. D.A.W. owns equity in BillionToOne, a company that provides non-invasive prenatal testing, and advises a fund with equity in Genome Medical. A.B. is a part-time senior advisor for primary care policy at the Center for Medicare and Medicaid Innovation, advising the Comprehensive Primary Care Plus and Primary Care First programs. R.C.G. has received consulting fees from AIA, Genomic Life, Grail, OptumLabs and Verily, and is co-founder and advisor to Genome Medical.

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Raoof, S., Kennedy, C.J., Wallach, D.A. et al. Molecular cancer screening: in search of evidence. Nat Med 27, 1139–1142 (2021).

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