Other suggested molecular mechanisms that may contribute to resistance to T-DM1 or T-DXd in cancer include the loss of solute carrier family 46 member 3 (SLC46A3), phosphatase and tensin homolog (PTEN) deficiency, caveolin 1 (CAV1) overexpression, multidrug resistance protein 1 (MDR1) expression, depletion of SLX4 structure-specific endonuclease subunit, and overexpression of voltage-dependent anion channel 3 (VDAC3)-derived circular RNA [[35], [36], [37], [38]]. This evidence concerns the gene PTEN and cancer.