(A) A schematic overview illustrating the strategy to score sensitivity and outgrowth of P18T parental, RASGAP knock out, and oncogenic mutant KRAS organoids of similar size during and after treatment with colorectal cancer (CRC) medium containing either DMSO, 1 μM afatinib (EGFRi), 1 μM selumetinib (MEKi), or a combination of 1 μM afatinib and 1 μM selumetinib. Organoid size and frequency of alive organoids was quantified after 72 hr of drug treatment and after 7 days of drug withdrawal by phenotypic analysis. (B) Representative zoom-in pictures of the parental patient-derived CRC organoids P18T KRASWT, KRASG12D, and P18T RASA1 (clone # 1 and # 3) or NF1 (# 6 and # 12) after 72 hours of DMSO or targeted drug treatment (on treatment). (C) Representative zoom-in pictures of the parental patient-derived CRC organoids P18T KRASWT, KRASG12D, and P18T RASA1 (clone # 1 and # 3) or NF1 (# 6 and # 12) after 7 days of DMSO or drug withdrawal (off treatment). Hoechst and DRAQ7 was used to visualize nuclei and dead cells, respectively.