The present disclosure teaches methods of treating a patient having an advanced metastatic cancer by administering a plurality of infusions of a first therapeutic agent comprising a tumor-targeted gene vector that encodes a cytocidal inhibitor of the CCNG1 gene product and a second therapeutic agent that affects the activity of at least one additional molecular target along the CCNG1 pathway. The additional molecular target may be Mdm2, PP2A, p53, Rb, c-Myc, or a cyclin-dependent kinase. The present disclosure also provides methods of treatment by administering a plurality of infusions of a first therapeutic agent comprising a tumor-targeted gene vector that encodes a cytocidal inhibitor of the CCNG1 gene product and a second therapeutic agent such as an immune-modulatory monoclonal antibody, a cytotoxic chemotherapeutic agent, an anti-angiogenesis agent, a selective tyrosine kinase inhibitor, or a monoclonal antibody directed against specific features of cells from the metastatic cancer. Further, the disclosure provides methods of treating a palpable tumor, methods for evaluating the role of oncogenic drivers along the Cyclin G1 pathway in a tumor, and methods of treatment that use such evaluations/analyses to guide the management of the disease.
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