Figure 4. Potential approach to deliver personalized combination therapies in real time.
Liquid biopsy and tumor samples are collected at diagnosis. A suite of CLIA assays are performed to establish the baseline tumor phenotype and genotype of the tumor and select an initial therapy. After a short treatment period, a second liquid biopsy and tumor samples are collected and re-analyzed. The on-treatment tumor phenotype and genotype is established and the therapy is reassessed for one of three scenarios. (1) If sensitivity to therapy is suspected, no changes are made in terms of treatment. (2) If targetable adaptive responses are induced, a second drug is added to generate a patient-specific combination therapy. (3) If the tumor is indifferent to therapy or displays acquired resistance, a new treatment will be selected. Importantly, during the whole process, the progression of the disease is monitored regularly. In case of progression, new samples are acquired and analyzed for therapy reassessment.