Oral HER2‑selective small‑molecule tyrosine kinase inhibitor that blocks HER2 kinase activity and downstream PI3K/AKT and MAPK signaling, with minimal EGFR inhibition and CNS activity.
Oral, HER2-selective tyrosine kinase inhibitor that binds the HER2 (ERBB2) kinase domain, inhibits autophosphorylation, and suppresses downstream PI3K/AKT and MAPK signaling, leading to growth inhibition and death of HER2-overexpressing tumor cells; minimal EGFR inhibition with CNS activity.
YES
DIRECT
Tucatinib binds the HER2 (ERBB2) kinase domain and blocks autophosphorylation, inhibiting PI3K/AKT and MAPK signaling, which leads to growth arrest and apoptosis of HER2-expressing tumor cells.
Oral HER2‑selective small‑molecule tyrosine kinase inhibitor that blocks HER2 kinase activity and downstream PI3K/AKT and MAPK signaling, with minimal EGFR inhibition and CNS activity.
Oral, HER2-selective tyrosine kinase inhibitor that binds the HER2 (ERBB2) kinase domain, inhibits autophosphorylation, and suppresses downstream PI3K/AKT and MAPK signaling, leading to growth inhibition and death of HER2-overexpressing tumor cells; minimal EGFR inhibition with CNS activity.
NO
INDIRECT
Tucatinib selectively inhibits HER2 (ERBB2) kinase; it has minimal EGFR inhibition, so EGFR-expressing cells are not directly targeted. Cell death occurs via HER2 pathway blockade, not EGFR engagement.
Humanized monoclonal antibody that binds the HER2 extracellular domain, inhibits receptor dimerization/signaling, promotes receptor downregulation, and mediates antibody‑dependent cellular cytotoxicity (ADCC).
Humanized monoclonal antibody that binds the HER2 (ERBB2) extracellular domain, blocks receptor dimerization and downstream signaling (PI3K/AKT, MAPK), promotes receptor downregulation, and mediates Fc-dependent ADCC against HER2-overexpressing tumor cells.
YES
DIRECT
Binds HER2 on target cells and engages Fc gamma receptor–bearing immune cells (e.g., NK cells) to trigger antibody-dependent cellular cytotoxicity (ADCC); may also activate complement.
Autologous patient T cells engineered to express a chimeric antigen receptor targeting CD19 on B cells; CAR engagement activates cytotoxic T-cell responses (activation, expansion, cytokine release, perforin/granzyme-mediated killing) to eliminate CD19+ malignant B cells and can cause on-target B-cell aplasia in pediatric r/r B-ALL.
Autologous patient T cells are engineered to express a chimeric antigen receptor that recognizes CD19 on B cells. CAR engagement triggers T-cell activation, proliferation, cytokine release, and perforin/granzyme-mediated cytotoxic killing of CD19-positive malignant B cells, often leading to on-target B-cell aplasia.
YES
DIRECT
CAR T cells bind CD19 on target cells and directly kill them via immunologic-synapse–mediated perforin/granzyme cytotoxicity (and death-receptor pathways), leading to apoptosis of CD19+ cells.
HER3-DXd; an antibody-drug conjugate composed of patritumab, a fully human anti-HER3 (ERBB3) IgG1 monoclonal antibody, linked via a cleavable tetrapeptide to deruxtecan (DXd), a membrane-permeable exatecan-derived topoisomerase I inhibitor. It binds HER3 on tumor cells, is internalized, and releases DXd in lysosomes to induce DNA single-strand breaks and apoptosis, with a bystander effect.
Fully human anti-HER3 (ERBB3) IgG1 antibody linked via a cleavable tetrapeptide to the topoisomerase I inhibitor DXd. Binds HER3 on tumor cells, is internalized, and releases DXd in lysosomes to inhibit topo I, causing DNA single-strand breaks and apoptosis, with a membrane-permeable bystander killing effect.
YES
DIRECT
The anti-HER3 ADC binds HER3, is internalized, and releases the topoisomerase I inhibitor DXd in lysosomes, causing DNA damage and apoptosis in the target cell, with additional bystander killing from the membrane-permeable payload.