Cancer biology as revealed by the research autopsy

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Abstract

A research autopsy is a post-mortem medical procedure performed on a deceased individual with the primary goal of collecting tissue to support basic and translational research. This approach has increasingly been used to investigate the pathophysiological mechanisms of cancer evolution, metastasis and treatment resistance. In this Review, we discuss the rationale for the use of research autopsies in cancer research and provide an evidence-based discussion of the quality of post-mortem tissues compared with other types of biospecimens. We also discuss the advantages of using post-mortem tissues over other types of biospecimens, including the large amounts of tissue that can be obtained and the extent of multiregion sampling that is achievable, which is not otherwise possible in living patients. We highlight how the research autopsy has supported the identification of the clonal origins and modes of spread among metastases, the extent that selective pressures imposed by treatments cause bottlenecks leading to parallel and convergent tumour evolution, and the creation of rare tissue banks and patient-derived model systems. Finally, we comment on the future of the research autopsy as an integral component of precision medicine strategies.

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Fig. 1: Methods and rationale for multiregion sampling.
Fig. 2: Multiregion sampling to understand the evolutionary biology of cancer.
Fig. 3: Interpretation of evolutionary dynamics relative to the sampling method.
Fig. 4: Incorporation of research autopsies into biomarker-driven adaptive clinical trials.
Fig. 5: Integration of multimodal data to maximize understanding of lethal cancer.

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Acknowledgements

The authors acknowledge grant support from the US National Institutes of Health (grants R01 CA179991 and R35 CA220508 to C.I.A,-D) and salary support from the Parker Institute for Cancer Immunotherapy to T.J.H.

Author information

All authors researched data for the manuscript and made substantial contributions to the discussion of the content. C.A.I.-D., J.E.H. and T.J.H. wrote the manuscript. C.A.I.-D., P.B., R.K., J.E.H. and T.J.H. reviewed and/or edited the manuscript before submission.

Correspondence to Christine A. Iacobuzio-Donahue.

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Competing interests

C.I.A.-D. and T.J.H. have received research support from Bristol-Myers Squibb. The other authors declare no competing interests.

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Nature Reviews Cancer thanks M. Rubin, S. Turajlic and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Rapid autopsy

An autopsy that is performed within 2 h of cardiopulmonary arrest.

Warm autopsy

An autopsy that is performed so rapidly that the deceased person’s body has not yet cooled to room temperature.

Somatic mosaicism

The presence of two or more genetically distinct populations of cells within an individual.

Tumour dormancy

A state in which viable cancer cells remain quiescent for a prolonged period.

Sanctuary sites

Tissues within the body in which cancer cells are protected from pharmacological agents or other therapies.

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