Developmental therapeutics for inflammatory breast cancer: Biology and translational directions

Abstract

Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, which accounts for approximately 3% of cases of breast malignancies. Diagnosis relies largely on its clinical presentation, and despite a characteristic phenotype, underlying molecular mechanisms are poorly understood. Unique clinical presentation indicates that IBC is a distinct clinical and biological entity when compared to non-IBC. Biological understanding of non-IBC has been extrapolated into IBC and targeted therapies for HER2 positive (HER2+) and hormonal receptor positive non-IBC led to improved patient outcomes in the recent years. This manuscript reviews recent discoveries related to the underlying biology of IBC, clinical progress to date and suggests rational approaches for investigational therapies.

Keywords: immunotherapy; inflammatory breast cancer; targeted therapy.

Figure 1. The Myc interaction with the cell cycle machinery

this figure is a simplified depiction of the role Myc oncoprotein in regulation of the cell cycle machinery. The normal cell replication processes are represented i.e., G1 first growth period to S DNA replication phase, G2 second growth period, and M, which is the mitosis period. Cyclin D2-CDK4 and CDK2 inactivate retinoblastoma protein (Rb) through phosphorylation. The latter event allows for cell cycle progression from G1 to S phase. Max/Myc complex targets cyclinD2-CDK4 complex formation ultimately stimulating cell cycle progression. Also cycle dependent kinase 2 (CDK2) complex activation is depicted through the abrogation of inhibitory action of Cki27 by active Max/Myc complex. When active CDK2 complex promotes initiation of S phase.