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Monitoring Trastuzumab Resistance and Cardiotoxicity: A Tale of Personalized Medicine.

Abstract While approval of trastuzumab, a recombinant monoclonal antibody directed against HER2, along with a diagnostic kit to detect breast cancers which are positive for HER2 overexpression, has advanced a new era of stratified and personalized medicine, it also created several challenges to our scientific and clinical practice. These problems include trastuzumab resistance and trastuzumab-induced cardiotoxicity. In this review, we will summarize data from the literature regarding mechanisms of trastuzumab resistance and trastuzumab-induced cardiotoxicity and present some promising model systems that may advance our understanding of these mechanisms. Our discussion will include development of circulating tumor cells and circulating tumor DNA for monitoring tumor burden, of patient-derived xenograft models for preclinical testing of novel therapies, and of novel therapeutic strategies for trastuzumab-resistance and possible integration of these strategies in the design of co-clinical studies for testing in relevant patient subpopulations.
PMID
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Authors

Mayor MeshTerms

Drug Resistance, Neoplasm

Precision Medicine

Keywords

Biomarkers

Breast cancer

Cardiotoxicity

HER2

HER2-positive breast cancer

Monoclonal antibody

Personalized medicine

Trastuzumab

Trastuzumab resistance

Trastuzumab-induced cardiotoxicity

Journal Title advances in clinical chemistry
Publication Year Start




PMID- 26231486
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20150803
IS  - 0065-2423 (Print)
IS  - 0065-2423 (Linking)
VI  - 70
DP  - 2015
TI  - Monitoring Trastuzumab Resistance and Cardiotoxicity: A Tale of Personalized
      Medicine.
PG  - 95-130
LID - 10.1016/bs.acc.2015.03.006 [doi]
LID - S0065-2423(15)00024-4 [pii]
AB  - While approval of trastuzumab, a recombinant monoclonal antibody directed against
      HER2, along with a diagnostic kit to detect breast cancers which are positive for
      HER2 overexpression, has advanced a new era of stratified and personalized
      medicine, it also created several challenges to our scientific and clinical
      practice. These problems include trastuzumab resistance and trastuzumab-induced
      cardiotoxicity. In this review, we will summarize data from the literature
      regarding mechanisms of trastuzumab resistance and trastuzumab-induced
      cardiotoxicity and present some promising model systems that may advance our
      understanding of these mechanisms. Our discussion will include development of
      circulating tumor cells and circulating tumor DNA for monitoring tumor burden, of
      patient-derived xenograft models for preclinical testing of novel therapies, and 
      of novel therapeutic strategies for trastuzumab-resistance and possible
      integration of these strategies in the design of co-clinical studies for testing 
      in relevant patient subpopulations.
CI  - Published by Elsevier Inc.
FAU - Dokmanovic, Milos
AU  - Dokmanovic M
AD  - Laboratory of Molecular Oncology, Division of Monoclonal Antibodies, Office of
      Biotechnology Products, Office of Pharmaceutical Science, Center for Drug
      Evaluation and Research, U.S. Food and Drug Administration, Silver Spring,
      Maryland, USA. Electronic address: [email protected]
FAU - Wu, Wen Jin
AU  - Wu WJ
AD  - Laboratory of Molecular Oncology, Division of Monoclonal Antibodies, Office of
      Biotechnology Products, Office of Pharmaceutical Science, Center for Drug
      Evaluation and Research, U.S. Food and Drug Administration, Silver Spring,
      Maryland, USA. Electronic address: [email protected]
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20150427
PL  - United States
TA  - Adv Clin Chem
JT  - Advances in clinical chemistry
JID - 2985173R
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA, Neoplasm)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antineoplastic Agents/adverse effects/*pharmacology/therapeutic use
MH  - Breast/drug effects/pathology
MH  - Breast Neoplasms/blood/complications/*drug therapy
MH  - Cardiotoxicity/complications/*etiology
MH  - DNA, Neoplasm/blood
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - *Precision Medicine
MH  - Trastuzumab/adverse effects/*pharmacology/therapeutic use
OTO - NOTNLM
OT  - Biomarkers
OT  - Breast cancer
OT  - Cardiotoxicity
OT  - HER2
OT  - HER2-positive breast cancer
OT  - Monoclonal antibody
OT  - Personalized medicine
OT  - Trastuzumab
OT  - Trastuzumab resistance
OT  - Trastuzumab-induced cardiotoxicity
EDAT- 2015/08/02 06:00
MHDA- 2016/02/03 06:00
CRDT- 2015/08/02 06:00
PHST- 2015/08/02 06:00 [entrez]
PHST- 2015/08/02 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
AID - S0065-2423(15)00024-4 [pii]
AID - 10.1016/bs.acc.2015.03.006 [doi]
PST - ppublish
SO  - Adv Clin Chem. 2015;70:95-130. doi: 10.1016/bs.acc.2015.03.006. Epub 2015 Apr 27.