Tumor cell profiling-based therapeutic targeting of cancer

A method of preparing a reference released tumor cell (RTC) profile library comprising:

• (i) isolating or enriching one or more released tumor cells (RTCs) from one or more biological samples one or more subjects to form isolated or enriched RTCs;
• (ii) expanding each of the one or more isolated or enriched RTCs in three-dimensional (3D) cell culture to form expanded RTCs;
• (iii) contacting or treating the expanded RTCs with one or more therapeutic agents or therapeutic modalities to identify expanded RTCs that are responsive to the one or more therapeutic agents or therapeutic modalities and expanded RTCs that are non-responsive to the one or more therapeutic agents or therapeutic modalities;
• and
• (iv) conducting molecular profiling, morphologic profiling, or both molecular profiling and morphologic profiling of the expanded RTCs that are responsive and the expanded RTCs that are non-responsive to the at least one therapeutic agent or therapeutic modality, thereby generating a reference RTC profile library.