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Pertuzumab

About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.


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Journal ArticleDOI
TL;DR: In this paper, the authors proposed a multi-modal strategy including both local treatment and systemic therapy to prevent and treat BMs from HER2+ breast cancer (BC), which represents an unmet clinical need.
Abstract: Brain metastases (BMs) are frequently associated with HER2+ breast cancer (BC). Their management is based on a multi-modal strategy including both local treatment and systemic therapy. Despite therapeutic advance, BMs still have an adverse impact on survival and quality of life and the development of effective systemic therapy to prevent and treat BMs from HER2 + BC represents an unmet clinical need. Trastuzumab-based therapy has long been the mainstay of systemic therapy and over the last two decades other HER2-targeted agents including lapatinib, pertuzumab and trastuzumab emtansine, have been introduced in the clinical practice. More recently, novel agents such as neratinib, tucatinib and trastuzumab deruxtecan have been developed, with interesting activity against BMs. Further research is needed to better elucidate the best sequence of these agents and their combination with local treatment.

8 citations

Journal ArticleDOI
12 May 2021
TL;DR: In this article, a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures.
Abstract: Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.

8 citations

Journal ArticleDOI
TL;DR: A large unmet need for strategies targeting novel signaling and resistance pathways is presented, and the HER2 pathway is targeted.
Abstract: TPS3620Background: Despite advances in systemic therapy, few patients are cured, creating a large unmet need for strategies targeting novel signaling and resistance pathways The HER2 pathway, whic

8 citations

Journal ArticleDOI
TL;DR: In this article, the authors evaluated the cost-effectiveness of pertuzumab with trastuzumaab biosimilar and docetaxel as initial treatment for HER2-positive metastatic breast cancer (MBC) in Singapore.
Abstract: This study evaluates the cost-effectiveness of pertuzumab with trastuzumab biosimilar and docetaxel as initial treatment for HER2-positive metastatic breast cancer (MBC) in Singapore.A partitioned ...

8 citations

Journal ArticleDOI
TL;DR: Most of the studies using biological agents to hit multiple targets in HER2-positive breast cancer patients confirm that resistance to single-agent Her2-targeting can be overcome and it is possible that newer molecular predictive factors may allow a more rationale choice of the most appropriate targeting for each individual patient.
Abstract: Introduction: Pharmacological targeting of the tyrosine kinase receptor HER2 with the monoclonal antibody trastuzumab has dramatically changed the outlook of HER2-positive breast cancer patients. However, HER2 is part of a more complex biological network that, when deregulated, plays a central role in sustaining the cancer phenotype. These interactions account for primary or acquired resistance to drugs that hit a single biological target, like trastuzumab. Several preclinical models suggest that simultaneous targeting of crucial metabolic pathways has the potential to circumvent or delay the onset of resistance phenomena in HER2-positive breast cancer cells. Areas covered: This review describes the rationale and results of clinical trials using biologically targeted agents in HER2-positive breast cancer patients. Single drugs that hit multiple targets and cocktails of biologically targeted agents are considered, whereas combinations with chemotherapy are not addressed. Expert opinion: Most of the studies...

8 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023372
2022307
2021158
2020144
2019143
2018130