1. Figure 1 A schematic representation of the HER2 signalling pathway
Figure 1 | A schematic representation of the HER2 signalling pathway. a | Circulating growth factors bind to the extracellular domain of EGFR growth factor receptor family members (such as EGFR, HER3, and IGF1R) inducing heterodimerization with the HER2 receptor. Dimerization induces phosphorylation of the kinase domain of HER2, which activates the PI3K/AKT and MAPK/MEK signalling pathways. Activation of these signalling pathways results in a downstream cascade that promotes the active transcription of genes involved in proliferation, angiogenesis, cell survival, and metastasis. b | The PI3K/AKT/mTOR signalling cascade is central to the growth-regulatory pathway in breast cancer. PTEN acts as a tumour suppressor, inhibiting the activation of Akt by PI3K. p27 inhibits transition through the cell cycle. Cyclin D1 can bind to p27, thereby interfering with its ability to suppress cellular proliferation. Signalling through the mTOR pathway regulates cell growth and proliferation, cellular metabolism, and angiogenesis, which are all essential for tumorigenesis. The mitogen-activated protein kinase (MAPK) pathway is also critical for cell growth and proliferation, and is frequently upregulated in cancer. Extensive crosstalk exists between the mTOR and MAPK pathways; both pathways can be activated by the same receptor-tyrosine kinases, dependent on the triggering ligand, and the pathways intersect at multiple points to regulate and coordinate signalling flux. Nodes in these pathways that are key therapeutic targets include receptor-tyrosine kinases that can be targeted using monoclonal antibodies and multikinase inhibitors, and rapalogues, which can be used to target mTOR. Expression of PTEN is often lost through genetic aberrations of PTEN. APC, antigen-presenting cell; FcγRIIIA, low affinity immunoglobulin gamma Fc region receptor III-A; WBC, white blood cell.
Gingras, I. et al. (2017) HER2‑positive breast cancer is lost in translation: time for patient-centered research
Nat. Rev. Clin. Oncol. doi: /nrclinonc