PMID- 34703436
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211028
IS  - 1662-6575 (Print)
IS  - 1662-6575 (Electronic)
IS  - 1662-6575 (Linking)
VI  - 14
IP  - 2
DP  - 2021 May-Aug
TI  - The Potential and Limitations of Precision Oncology: Lessons Learned from 
      Whole-Exome Sequencing in an Exceptional Response to Everolimus in Advanced Renal 
      Cell Carcinoma.
PG  - 1194-1200
LID - 10.1159/000516277 [doi]
AB  - Through elucidating the genetic mechanisms of drug sensitivity, precision 
      medicine aims to improve patient selection and response to therapy. Exceptional 
      responders are patients that exhibit exquisite and durable responses to targeted 
      therapy, providing a rare opportunity to identify the molecular basis of drug 
      sensitivity. We identified an exceptional responder to everolimus, an oral 
      inhibitor of the mammalian target of rapamycin (mTOR) pathway, in a patient with 
      advanced renal cell carcinoma. Through whole-exome sequencing on pretreatment and 
      metastatic tumor DNA, we identified alterations in several mTOR pathway genes, 
      with several mutations implicated in mTOR activation. Importantly, these 
      alterations are currently not included in commercially available next-generation 
      sequencing panels, suggesting that precision medicine is still limited in its 
      ability to predict responses to mTOR-targeted therapies. Further research to 
      discover and validate predictive biomarkers of response to everolimus and other 
      targeted therapies is urgently needed. Given the rarity of patients with 
      exceptional responses to targeted agents, cooperative efforts to understand the 
      molecular basis for these phenotypes are essential.
CI  - Copyright (c) 2021 by S. Karger AG, Basel.
FAU - Pilling, Amanda
AU  - Pilling A
AD  - Department of Internal Medicine, Henry Ford Health System, Henry Ford Cancer 
      Institute, Detroit, Michigan, USA.
FAU - Wee, Christopher
AU  - Wee C
AD  - Department of Medicine, Wayne State University School of Medicine, Detroit, 
      Michigan, USA.
FAU - Bar-Meir, Eliezer
AU  - Bar-Meir E
AD  - Department of Medicine, Wayne State University School of Medicine, Detroit, 
      Michigan, USA.
FAU - Dyson, Gregory
AU  - Dyson G
AD  - Department of Oncology, Population Statistics, Wayne State University School of 
      Medicine, Detroit, Michigan, USA.
FAU - Hwang, Ok
AU  - Hwang O
AD  - Department of Internal Medicine, Henry Ford Health System, Henry Ford Cancer 
      Institute, Detroit, Michigan, USA.
FAU - Gupta, Nilesh
AU  - Gupta N
AD  - Department of Pathology, Henry Ford Health System, Henry Ford Cancer Institute, 
      Detroit, Michigan, USA.
FAU - Chitale, Dhananjay
AU  - Chitale D
AD  - Department of Pathology, Henry Ford Health System, Henry Ford Cancer Institute, 
      Detroit, Michigan, USA.
FAU - Hwang, Clara
AU  - Hwang C
AD  - Department of Internal Medicine, Henry Ford Health System, Henry Ford Cancer 
      Institute, Detroit, Michigan, USA.
LA  - eng
PT  - Case Reports
DEP - 20210816
PL  - Switzerland
TA  - Case Rep Oncol
JT  - Case reports in oncology
JID - 101517601
PMC - PMC8460888
OTO - NOTNLM
OT  - Biomarker
OT  - Durable response
OT  - Mammalian target of rapamycin inhibitor
COIS- The authors declare no conflicts of interest.
EDAT- 2021/10/28 06:00
MHDA- 2021/10/28 06:01
PMCR- 2021/08/16
CRDT- 2021/10/27 07:06
PHST- 2021/03/22 00:00 [received]
PHST- 2021/03/30 00:00 [accepted]
PHST- 2021/10/27 07:06 [entrez]
PHST- 2021/10/28 06:00 [pubmed]
PHST- 2021/10/28 06:01 [medline]
PHST- 2021/08/16 00:00 [pmc-release]
AID - cro-0014-1194 [pii]
AID - 10.1159/000516277 [doi]
PST - epublish
SO  - Case Rep Oncol. 2021 Aug 16;14(2):1194-1200. doi: 10.1159/000516277. eCollection 
      2021 May-Aug.