Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer

Dena P. Rhinehart; Jiaying Lai; David E. Sanin; Varsha Vakkala; Adrianna Mendes; Christopher Bailey; Emmanuel Antonarakis; Channing J. Paller; Xiaojun Wu; Tamara L. Lotan; Rachel Karchin; Laura A. Sena

doi:10.1038/s41698-024-00773-w

Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer

Dena P. Rhinehart, Jiaying Lai, David E. Sanin, Varsha Vakkala, Adrianna Mendes, Christopher Bailey, Emmanuel Antonarakis, Channing J. Paller, Xiaojun Wu, Tamara L. Lotan, Rachel Karchin, Laura A. Sena

Research output: Contribution to journal › Article › peer-review

Abstract

Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary resistance. Direct demonstration of the latter mechanism in patients with PCa is lacking. Here we present a case report as proof-of-principle that outgrowth of a subpopulation of cancer cells lacking the genomic target and present prior to therapy initiation can drive acquired resistance to targeted therapy and threaten survival in patients with PCa.

Original language	English (US)
Article number	275
Journal	npj Precision Oncology
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41698-024-00773-w
State	Published - Dec 2024
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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title = "Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer",

abstract = "Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary resistance. Direct demonstration of the latter mechanism in patients with PCa is lacking. Here we present a case report as proof-of-principle that outgrowth of a subpopulation of cancer cells lacking the genomic target and present prior to therapy initiation can drive acquired resistance to targeted therapy and threaten survival in patients with PCa.",

author = "Rhinehart, {Dena P.} and Jiaying Lai and Sanin, {David E.} and Varsha Vakkala and Adrianna Mendes and Christopher Bailey and Emmanuel Antonarakis and Paller, {Channing J.} and Xiaojun Wu and Lotan, {Tamara L.} and Rachel Karchin and Sena, {Laura A.}",

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doi = "10.1038/s41698-024-00773-w",

language = "English (US)",

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T1 - Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer

AU - Rhinehart, Dena P.

AU - Lai, Jiaying

AU - Sanin, David E.

AU - Vakkala, Varsha

AU - Mendes, Adrianna

AU - Bailey, Christopher

AU - Antonarakis, Emmanuel

AU - Paller, Channing J.

AU - Wu, Xiaojun

AU - Lotan, Tamara L.

AU - Karchin, Rachel

AU - Sena, Laura A.

PY - 2024/12

Y1 - 2024/12

N2 - Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary resistance. Direct demonstration of the latter mechanism in patients with PCa is lacking. Here we present a case report as proof-of-principle that outgrowth of a subpopulation of cancer cells lacking the genomic target and present prior to therapy initiation can drive acquired resistance to targeted therapy and threaten survival in patients with PCa.

AB - Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary resistance. Direct demonstration of the latter mechanism in patients with PCa is lacking. Here we present a case report as proof-of-principle that outgrowth of a subpopulation of cancer cells lacking the genomic target and present prior to therapy initiation can drive acquired resistance to targeted therapy and threaten survival in patients with PCa.

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Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer

Abstract

ASJC Scopus subject areas

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