Neu Perspectives, Therapies, and Challenges for Metastatic HER2-Positive Breast Cancer

Even though gene amplification or protein overexpression occurs in approximately one-fifth of all breast cancers, the discovery of HER2 has, nevertheless, had profound implications for the disease. Indeed, the characterization of the receptor resulted in a number of significant advances. Structurall...

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Bibliographic Details
Published in:Breast cancer targets and therapy 2021-01, Vol.13, p.539-557
Main Authors: Salkeni, Mohamad Adham, Rizvi, Wajeeha, Hein, Kyaw, Higa, Gerald M
Format: Article
Language:English
Subjects:
Adjuvant treatment
ado-trastuzumab emtansine
Antimitotic agents
Antineoplastic agents
Breast cancer
Cancer
Cell cycle
Cell surface
Cellular signal transduction
Chemotherapy
Clinical trials
Cyclin-dependent kinases
Development and progression
Disease resistance
erbb
ErbB-2 protein
fam-trastuzumab deruxtecan
Gene amplification
Gene expression
Growth factors
her2
Immune system
Immunotherapy
Innate immunity
Kinases
lapatinib
Ligands
margetuximab
Metastases
Metastasis
Monoclonal antibodies
neratinib
neu
pertuzumab
phesgo
Phosphorylation
Prognosis
Proteins
Review
Sarcoma
Signal transduction
Targeted cancer therapy
trastuzumab
tucatinib
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Summary:Even though gene amplification or protein overexpression occurs in approximately one-fifth of all breast cancers, the discovery of HER2 has, nevertheless, had profound implications for the disease. Indeed, the characterization of the receptor resulted in a number of significant advances. Structurally, unique features provided avenues for the development of numerous compounds with target-specificity; molecularly, biological constructs revealed a highly complex, internal signal transduction pathway with regulatory effects on tumor proliferation, survival, and perhaps, even resistance; and clinically, disease outcomes manifested its predictive and prognostic value. Yet despite the receptor's utility, the beneficial effects are diminished by tumor recurrence after neo- or adjuvant therapy as well as losses resulting from the inability to cure patients with metastatic disease. What these observations suggest is that while tumor response may be partially linked to uncoupling cell surface message reception and nuclear gene expression, as well as recruitment of the innate immune system, disease progression and/or resistance may involve a reprogrammable signaling mainframe that elicits alternative growth and survival signals. This review attempts to meld current perceptions related to HER2-positive metastatic breast cancer with particular attention to current biological insights and therapeutic challenges. Keywords: ado-trastuzumab emtansine, ErbB, Fam-trastuzumab deruxtecan, HER2, lapatinib, margetuximab, neratinib, neu, pertuzumab, PHESGO, trastuzumab, tucatinib
ISSN:1179-1314
1179-1314
DOI:10.2147/BCTT.S288344