The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer

The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of therapeutic responses, there has been an explosion of research into the mechanisms of microbial effects on CRC. Harnessing and reprogramming the microbiome may allow for the expansion of these successes to broader categories of CRC, the prevention of CRC in high-risk patients, and the enhancement of standard treatments. In this review, we pull together both well-documented phenomena and recent discoveries that pertain to the microbiome and CRC. We explore the microbial mechanisms associated with CRC pathogenesis and progression, recent advancements in CRC systemic therapy, potential options for diagnosis and prevention, as well as directions for future research

Sphingosine-1-Phosphate Transporters as Targets for Cancer Therapy

Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that regulates cell survival, migration, the recruitment of immune cells, angiogenesis, and lymphangiogenesis, all of which are involved in cancer progression. S1P is generated inside cancer cells by sphingosine kinases then exported outside of the cell into the tumor microenvironment where it binds to any of five G protein coupled receptors and proceeds to regulate a variety of functions. We have recently reported on the mechanisms underlying the “inside-out” signaling of S1P, its export through the plasma membrane, and its interaction with cell surface receptors. Membrane lipids, including S1P, do not spontaneously exchange through lipid bilayers since the polar head groups do not readily go through the hydrophobic interior of the plasma membrane. Instead, specific transporter proteins exist on the membrane to exchange these lipids. This review summarizes what is known regarding S1P transport through the cell membrane via ATP-binding cassette transporters and the spinster 2 transporter and discusses the roles for these transporters in cancer and in the tumor microenvironment. Based on our research and the emerging understanding of the role of S1P signaling in cancer and in the tumor microenvironment, S1P transporters and S1P signaling hold promise as new therapeutic targets for cancer drug development