Cancers, Vol. 11, Pages 902: The d16HER2 Splice Variant: A Friend or Foe of HER2-Positive Cancers?

Cancers, Vol. 11, Pages 902: The d16HER2 Splice Variant: A Friend or Foe of HER2-Positive Cancers? Cancers doi: 10.3390/cancers11070902 Authors: Lorenzo Castagnoli Michael Ladomery Elda Tagliabue Serenella M. Pupa Human epidermal growth factor receptor 2 (ERBB2 or HER2) amplification/overexpression is associated with a particularly aggressive molecular subtype of breast cancer (BC), characterized by a poor prognosis, increased metastatic potential, and disease recurrence. As only approximately 50% of HER2-positive patients respond to HER2-targeted therapies, greater knowledge of the biology of HER2 and the mechanisms that underlie drug susceptibility is needed to improve cure rates. Evidence suggests that the coexistence of full-length, wild-type HER2 (wtHER2) and altered forms of HER2—such as carboxy-terminus-truncated fragments, activating mutations, and splice variants—significantly increases the heterogeneity of HER2-positive disease, affecting its biology, clinical course, and treatment response. In particular, expression of the d16HER2 splice variant in human HER2-positive BC has a crucial pathobiological function, wherein the absence of sixteen amino acids from the extracellular domain induces the formation of stable and constitutively active HER2 homodimers on the tumor cell surface. Notably, the d16HER2 variant significantly influences the initiation and aggressiveness of tumors, cancer stem cell properties, epithelial&am...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research