An omic and multidimensional spatial atlas from serial biopsies of an evolving metastatic breast cancer.
human tumor atlas
metastatic breast cancer
personalized medicine
precision oncology
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
15 02 2022
15 02 2022
Historique:
received:
07
07
2021
revised:
15
11
2021
accepted:
19
01
2022
entrez:
4
3
2022
pubmed:
5
3
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells and extrinsic microenvironmental influences change during treatment. To support the development of methods for identifying these mechanisms in individual people, here we present an omic and multidimensional spatial (OMS) atlas generated from four serial biopsies of an individual with metastatic breast cancer during 3.5 years of therapy. This resource links detailed, longitudinal clinical metadata that includes treatment times and doses, anatomic imaging, and blood-based response measurements to clinical and exploratory analyses, which includes comprehensive DNA, RNA, and protein profiles; images of multiplexed immunostaining; and 2- and 3-dimensional scanning electron micrographs. These data report aspects of heterogeneity and evolution of the cancer genome, signaling pathways, immune microenvironment, cellular composition and organization, and ultrastructure. We present illustrative examples of how integrative analyses of these data reveal potential mechanisms of response and resistance and suggest novel therapeutic vulnerabilities.
Identifiants
pubmed: 35243422
doi: 10.1016/j.xcrm.2022.100525
pii: S2666-3791(22)00025-8
pmc: PMC8861971
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100525Subventions
Organisme : NCI NIH HHS
ID : P30 CA069533
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA231877
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA224012
Pays : United States
Organisme : NCI NIH HHS
ID : U2C CA233280
Pays : United States
Organisme : NCI NIH HHS
ID : R44 CA224994
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209988
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217842
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM132322
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
D.S. is employed by Quantitative Imaging Systems. L.M.C. is a paid consultant for Cell Signaling Technologies, Shasqi, and AbbVie; received reagent and/or research support from Plexxikon, Pharmacyclics, Acerta Pharma, Deciphera Pharmaceuticals, Genentech, Roche Glycart AG, Syndax Pharmaceuticals, Innate Pharma, and NanoString Technologies; and is a member of the scientific advisory boards of Syndax Pharmaceuticals, Carisma Therapeutics, Zymeworks, Verseau Therapeutics, Cytomix Therapeutics, and Kineta. G.B.M. has licensed technologies to Myriad Genetics and NanoString; is on the SAB or is a consultant to Amphista, AstraZeneca, Chrysallis Biotechnology, GSK, ImmunoMET, Ionis, Lilly, PDX Pharmaceuticals, Signalchem Lifesciences, Symphogen, Tarveda, Turbine, and Zentalis Pharmaceuticals; and has stock/options/financial interests in Catena Pharmaceuticals, ImmunoMet, SignalChem, and Tarveda. J.W.G. has licensed technologies to Abbott Diagnostics, Zorro Bio, and PDX Pharmaceuticals; has ownership positions in Convergent Genomics, Health Technology Innovations, Zorro Bio, and PDX Pharmaceuticals; serves as a paid consultant to New Leaf Ventures; has received research support from Thermo Fisher Scientific (formerly FEI), Zeiss, Miltenyi Biotech, Cepheid (Danaher), Quantitative Imaging, Health Technology Innovations, and Micron Technologies; and owns stock in Abbott Diagnostics, AbbVie, Alphabet, Amazon, Amgen, Apple, General Electric, Gilead, Intel, Microsoft, Nvidia, and Zimmer Biomet.
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