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In patients with colorectal cancer (CRC) that metastasizes to the liver, there are several key goals for improving outcomes including early detection, effective prognostic indicators of treatment response, and accurate identification of patients at high risk for recurrence. Although new therapeutic regimens developed over the past decade have increased survival, there is substantial room for improvement in selecting targeted treatment regimens for the patients who will derive the most benefit. Recently, there have been exciting developments in identifying high-risk patient cohorts, refinements in the understanding of systemic vs localized drug delivery to metastatic niches, liquid biomarker development, and dramatic advances in tumor immune therapy, all of which promise new and innovative approaches to tackling the problem of detecting and treating the metastatic spread of CRC to the liver. Our multidisciplinary group held a state-of-the-science symposium this past year to review advances in this rapidly evolving field. Herein, we present a discussion around the issues facing treatment of patients with CRC liver metastases, including the relationship of discrete gene signatures with prognosis. We also discuss the latest advances to maximize regional and systemic therapies aimed at decreasing intrahepatic recurrence, review recent insights into the tumor microenvironment, and summarize advances in noninvasive multimodal biomarkers for early detection of primary and recurrent disease. As we continue to advance clinically and technologically in the field of colorectal tumor biology, our goal should be continued refinement of predictive and prognostic studies to decrease recurrence after curative resection and minimize treatment toxicity to patients through a tailored multidisciplinary approach to cancer care.

Numerous animal studies and recent clinical studies have shown that electroporation-delivered DNA vaccines can elicit robust Ag-specific CTL responses and reduce disease severity. However, cancer antigens are generally poorly immunogenic, requiring special conditions for immune response induction. To date, many different approaches have been used to elicit Ag-specific CTL and anti-neoplastic responses to DNA vaccines against cancer. In vivo electroporation is one example, whereas others include DNA manipulation, xenogeneic antigen use, immune stimulatory molecule and immune response regulator application, DNA prime-boost immunization strategy use and different DNA delivery methods. These strategies likely increase the immunogenicity of cancer DNA vaccines, thereby contributing to cancer eradication. However, cancer cells are heterogeneous and might become CTL-resistant. Thus, understanding the CTL resistance mechanism(s) employed by cancer cells is critical to develop counter-measures for this immune escape. In this review, the use of electroporation as a DNA delivery method, the strategies used to enhance the immune responses, the cancer antigens that have been tested, and the escape mechanism(s) used by tumor cells are discussed, with a focus on the progress of clinical trials using cancer DNA vaccines.