Genomic sequencing of a tumor to guide Individualized treatments for cancer, often called personalized medicine or precision oncology, holds great promise for improving cancer management. The hope is that we can identify key genetic mutations in every tumor then exploit that knowledge to prescribe treatments specifically targeted to those mutations. While theoretically simple, the reality is more complex. Many tumors have multiple mutations, and it is not clear which mutation or combination of mutations is most critical. Some mutations are attractive targets for treatment but lack good drugs to target them with. We have developed an integrated approach that combines genomic analytics and experimental validation to provide additional treatment options to patients that fail standard of care. A combination of MPseq, RNAseq and WES constitute our genomics approach. MPseq is a process that provides a detailed description of all DNA rearrangements at a resolution that can show how individual genes are disturbed thus providing necessary novel insight for correct clinical interpretation. The technologies and protocols developed allow for the genomic evaluation of biopsies. The potential detection of targetable rearrangements and mutations cross-validated by RNAseq provides relatively robust evidence that the associated pathways are targetable. Related drugs can then be validated experimentally in 3D-culture model systems, termed microtumors. The combination of the above processes could provide reasonable indication to oncologists to act.