 This study investigated the clonal dynamics of chemotherapy-induced drug resistance in colon cancer cells. Bar-coating technology was used to track the development of drug-resistant variants over time, which revealed polyclinality in the development of resistance. Additionally, collateral drug testing identified several drugs that could be used as second-line treatments for drug-resistant colon cancer cells. This article was authored by Narcita Danisic, Kubra Selikbazilmaz, and Ahmed Akhar.