Retinitis pigmentosa (RP) is a heterogeneous genetic disorder that is characterized by a progressive loss of photoreceptors that results in deterioration of vision. While gene therapy has shown promise for some forms of RP, over 60 genes have been implicated in this disorder; therefore, non-gene-targeted therapies are of great interest. In this episode, Stephen Tsang and colleagues discuss their study, which shows that upregulation of glycolytic flux, via targeted downregulation of sirtuin 6, in rod photoreceptors improves photoreceptor survival and preserves vision in a mouse model of RP. As this strategy is not gene-specific, it may be beneficial for a range of neurodegenerative disorders.
Cancer cells have a different response to nutrient limitation than healthy cells; therefore, targeting nutrient acquisition pathways has potential as a therapeutic strategy for limiting cancer cell growth. In this episode, Aimee Edinger discusses a recent study from her group, which describes the effects of a sphingolipid-based compound, SH-BC-893, in multiple pre-clinical cancer models. SH-BC-893 simultaneously disrupts both glucose and amino acid transporters and was effective against both rapid- and slow-growing tumors without affecting normal tissues. The results of this study support further exploration of the therapeutic potential of this compound.
There is substantial crosstalk between tumor cells and surrounding stromal cell populations, and the specific microenvironment of a tumor greatly influences progression, malignancy, metastasis, plasticity, and therapeutic response. In this episode, Michael Stürzl, Elisabeth Naschberger, and Andrea Liebl discuss their study, which identifies endothelial cell secretion of the protein SPARCL1 as an important regulator of colorectal cancer aggressiveness. SPARCL1 expression was increased in endothelial cells from normal colon and in tumor endothelial cells that were isolated from patients with a favorable prognosis and dramatically reduced in tumor endothelial cells from patients with aggressive colorectal carcinoma. Together, the results of this study indicate that endothelial cell-derived SPARCL1 promotes an antitumorigenic microenvironment by inducing cell quiescence and limiting angiogenesis.
Ovarian cancer is difficult to diagnose at early stages, and once it has metastasized, it is associated with a very high mortality rate. During transcoelomic metastasis, ovarian tumor cells detach from the primary tumor site and migrate to the peritoneal cavity, where their survival is supported by tumor-associated macrophages (TAMs). In the accompanying video, Yale University professor Wang Min describes how TAMs are recruited to ovarian tumor cells in the peritoneal environment to form spheroids that drive the early stages of metastasis. His recent study, published this week in the JCI, has shown that tumors attract macrophages by releasing cytokines. The macrophages then secrete growth factors such as EGF that promote tumor cell adhesion and proliferation, leading to the formation of tumor cell spheroids. This work elucidates a mechanism that may be a useful therapeutic target for treating ovarian and other transcoelomic metastatic cancers.