Table 1.

Molecular mechanisms of resistance to anti-HER2 therapies.

Mechanism	Description	Ref
Signaling from other HER receptors	Activation of HER3 or EGFR can bypass HER2 blockade, sustaining growth.	[8]
Activation of PI3K/AKT/mTOR pathways	Promotes cell survival and proliferation, contributing to resistance.	[9]
C-MET overexpression	Activates alternative pathways, enhancing tumor survival.	[10]
Loss of PTEN	Leads to increased PI3K signaling, promoting tumor growth.	[11]
Upregulation of Src activity	Enhances tumor cell proliferation and survival through various pathways.	[12]
MUC4 expression	Inhibits binding of trastuzumab to HER2, reducing its efficacy.	[13]
Expression of p95 HER2 isoform	Lacks trastuzumab binding site, allowing continued signaling.	[14]