Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses

SIMPLE SUMMARY: Triple-negative breast cancer (TNBC) is an aggressive as well as the most dangerous form of breast cancer. Due to the lack of biomarkers that can be targeted by specific molecular therapeutics, treatment is usually limited to chemotherapy and surgery where applicable. Oncolytic viruses are biologicals that have been engineered in many cases to express different genes that can aid in the recruitment of immune cells to trigger antitumor immune responses in addition to the direct lysis of infected cancerous cells. In this review, the basic biology of TNBC is described, as are the many OVs and their different strategies to attempt to treat TNBC in vitro, in vivo, and in human trials. ABSTRACT: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-fifth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difficulty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to other breast cancers. Tumor heterogeneity also poses a large obstacle to treatment approaches. No driver of tumor development has been identified for TNBC, and large variations in mutational burden between tumors have been described previously. Here, we describe the biology of six different subtypes of TNBC, based on differential gene expression. Subtype differences can have a large impact on metastatic potential and resistance to treatment. Emerging antibody-based therapeutics, such as immune checkpoint inhibitors, have available targets for small subsets of TNBC patients, leading to partial responses and relatively low overall efficacy. Immuno-oncolytic viruses (OVs) have recently become significant in the pursuit of effective treatments for TNBC. OVs generally share the ability to ignore the heterogeneous nature of TNBC cells and allow infection throughout a treated tumor. Recent genetic engineering has allowed for the enhancement of efficacy against certain tumor types while avoiding the most common side effects in non-cancerous tissues. In this review, TNBC is described in order to address the challenges it presents to potential treatments. The OVs currently described preclinically and in various stages of clinical trials are also summarized, as are their strategies to enhance therapeutic potential.