Colorectal cancer is a disease with high unmet medical needs. An increase in the number of cancer patients who are resistant to anti-cancer drugs is one of factors that increase the number of fatalities. Since there was no suitable experimental model to recapitulate the tumor environment in which various cells in the tissues exist, it was extremely difficult to develop a medicine that overcomes the anti-cancer drug resistance in each colorectal cancer patient. In this review, we describe the current status and problems of drug therapy for colorectal cancer patients, and introduce our study to develop the new targeting drugs using human colon tissue-derived air liquid interface organoid culture method.