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Targeting minimal residual disease: a path to cure?

Abstract

Therapeutics that block kinases, transcriptional modifiers, immune checkpoints and other biological vulnerabilities are transforming cancer treatment. As a result, many patients achieve dramatic responses, including complete radiographical or pathological remission, yet retain minimal residual disease (MRD), which results in relapse. New functional approaches can characterize clonal heterogeneity and predict therapeutic sensitivity of MRD at a single-cell level. Preliminary evidence suggests that iterative detection, profiling and targeting of MRD would meaningfully improve outcomes and may even lead to cure.

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Figure 1: Paradigms for management of MRD.
Figure 2: Current paradigm for management of MRD in patients with acute lymphoblastic leukaemia.
Figure 3: Suspended microchannel resonator and workflow for the mass accumulation rate assay.

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Acknowledgements

The authors thank C. Love and M. Stevens for thoughtful review and comments. D.M.W. and S.R.M. are supported by the Koch Institute–Dana-Farber/Harvard Cancer Center Bridge Project, the National Cancer Institute (NCI) R33 CA191143 and the NCI Cancer Systems Biology Consortium U54 CA217377. D.M.W. is a Leukaemia and Lymphoma Society Scholar. M.A.M. is supported by NCI K08 CA212252.

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M.R.L, M.A.M., S.R.M. and D.M.W. researched data for the article, substantially contributed to discussion of content, wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Scott R. Manalis or David M. Weinstock.

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D.M.W. declares that he is a consultant for and receives research funding from Novartis and is a founder of Travera. S.R.M. declares that he is a founder of Affinity Biosensors and a founder and scientific adviser of Travera. The other authors declare no competing interests.

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Luskin, M., Murakami, M., Manalis, S. et al. Targeting minimal residual disease: a path to cure?. Nat Rev Cancer 18, 255–263 (2018). https://doi.org/10.1038/nrc.2017.125

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