a | Activating Cre in a tissue-specific manner, by either viral delivery or Cre-oestrogen response element (ERE)-mediated tamoxifen administration. Examples are shown for lung cancer7 and ovarian cancer12, and melanoma11. b | Tetracycline (Tet)-mediated transgene inactivation or activation by doxycycline administration or withdrawal using the Tet-On or Tet-Off systems. Examples are shown for liver cancer22 and melanoma5. fl, flox; lsl, lox-STOP-lox; rtTA, reverse transactivator; tTA, transactivator.