Therapies aiming at molecular targets significantly increased the efficacy of cancer treatment. However, in many instances, resistance develops and leads to progression of the disease. Development of resistance and recurrence is often due to intratumor heterogeneity, that drives evolution of the tumor during treatment. Genetically, epigenetically or phenotypically distinct subpopulations of cancer cells within a tumor can respond differently to therapy due to variable expression of the treatment target or presence of resistance-conferring mutations. Treatment-associated changes arising within the microenvironment of a growing tumor mass, such as nutrient and oxygen supply, often select for more opportunistic cells. Therefore, designing better methods of detection of rare resistant cells in treatment-naïve tumor samples and understanding of the cellular selection processes would help predict patient outcomes and guide future therapies. We aim to uncover the functional relevance of genetic intratumor heterogeneity in development of treatment resistance, which will allow us to design methods for early detection of resistance-conferring clones in heterogeneous tumors.