Magic™ Anti-PhosphoY (Phospho Y) polyclonal antibody

Menin serves both tumor suppressor and promoter roles in a highly tumor-specific manner. In colorectal cancer, menin is over-expressed and plays a critical role in regulating transcription of SKP2, and combined treatment with a menin inhibitor and smallmolecule EGFR inhibitor (EGFRi) leads to synergistic killing of colorectal cancer cells. However, the full spectrum of menin function in colorectal cancer remains uncertain. Herein, we demonstrate that menin inhibition increases glycolysis in colorectal cancer cells. This menin inhibitor-induced increase in glycolysis occurs in an mTOR-independent manner and enhances the sensitivity of colorectal cancer cells to EGFRis. In addition, we show that EGFRis induce autophagy in colorectal cancer cells, which is important for cell survival in the setting of combined treatment with an EGFRi and menin inhibitor. Inhibition of autophagy with chloroquine further sensitizes colorectal cancers to treatment with the combination of an EGFRi and menin inhibitor. Together, these findings uncover a novel role for menin in colorectal cancer as a repressor of glycolysis and demonstrate that menin inhibitor-induced increases in glycolysis sensitize colorectal cancer cells to EGFRis. In addition, these findings illustrate the importance of autophagy as a protective mechanism against EGFRis, especially in the presence of menin inhibition. Ultimately, these data open the possibility of using menin-mediated regulation of glycolysis to potentially improve treatment modalities for colorectal cancer.

Body composition refers to the proportional content of body fat mass and lean body mass that can lead to a continuum of different phenotypes ranging from cachectic/sarcopenic state to obesity. The heterogenetic phenotypes of body composition can contribute to formation of some cancer types and can sometimes lead to disparate outcomes. Both of these extremes of the spectrum exist in patients with non-small cell lung carcinoma (NSCLC). The discovery of new pathways that drive tumorigenesis contributing to cancer progression and resistance have expanded our understanding of cancer biology leading to development of new targeted therapies including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) that have changed the landscape of NSCLC treatment. However, in the new era of precision medicine, the impact of body composition phenotypes on treatment outcomes and survival is now being elucidated. In this review, we will discuss the emerging evidence of a link between body composition and outcomes in patients with NSCLC treated with TKI and ICI. We will also discuss suggested mechanisms by which body composition can impact tumor behavior and anti-tumor immunological response.