Deep learning classification of ex vivo human colon tissues using spectroscopic optical coherence tomography.

Screening for colorectal cancer (CRC) with colonoscopy has improved patient outcomes; however, it remains the third leading cause of cancer-related mortality, novel strategies to improve screening are needed. Here, we propose an optical biopsy technique based on spectroscopic optical coherence tomography (OCT). Depth resolved OCT images are analyzed as a function of wavelength to measure optical tissue properties and used as input to machine learning algorithms. Previously, we used this approach to analyze mouse colon polyps. Here, we extend the approach to examine human biopsied colonic epithelial tissue samples ex vivo. Optical properties are used as input to a novel deep learning architecture, producing accuracy of up to 97.9% in discriminating tissue type. SOCT parameters are used to create false colored en face OCT images and deep learning classifications are used to enable visual classification by tissue type. This study advances SOCT toward clinical utility for analysis of colonic epithelium.

Asparagine synthetase and G-protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer.

Survival differences exist in colorectal cancer (CRC) patients by sex and disease stage. However, the potential molecular mechanism(s) are not well understood. Here we show that asparagine synthetase (ASNS) and G protein-coupled estrogen receptor-1 (GPER1) are critical sensors of nutrient depletion and linked to poorer outcomes for females with CRC. Using a 3D spheroid model of isogenic SW48 KRAS wild-type (WT) and G12A mutant (MT) cells grown under a restricted nutrient supply, we found that glutamine depletion inhibited cell growth in both cell lines, whereas ASNS and GPER1 expression were upregulated in KRAS MT versus WT. Estradiol decreased growth in KRAS WT but had no effect on MT cells. Selective GPER1 and ASNS inhibitors suppressed cell proliferation with increased caspase-3 activity of MT cells under glutamine depletion condition particularly in the presence of estradiol. In a clinical colon cancer cohort from The Cancer Genome Atlas, both high GPER1 and ASNS expression were associated with poorer overall survival for females only in advanced stage tumors. These results suggest KRAS MT cells have mechanisms in place that respond to decreased nutrient supply, typically observed in advanced tumors, by increasing the expression of ASNS and GPER1 to drive cell growth. Furthermore, KRAS MT cells are resistant to the protective effects of estradiol under nutrient deplete conditions. The findings indicate that GPER1 and ASNS expression, along with the interaction between nutrient supply and KRAS mutations shed additional light on the mechanisms underlying sex differences in metabolism and growth in CRC, and have clinical implications in the precision management of KRAS mutant CRC.

Colorectal Cancer Immunotherapy: State of the Art and Future Directions.

Cancer immunotherapy has become an indispensable mode of treatment for a multitude of solid tumor cancers. Colorectal cancer (CRC) has been one of the many cancer types to benefit from immunotherapy, especially in advanced disease where standard treatment fails to prevent recurrence or results in poor survival. The efficacy of immunotherapy in CRC has not been without challenge, as early clinical trials observed dismal responses in unselected CRC patients treated with checkpoint inhibitors. Many studies and clinical trials have since refined immunotherapies available for CRC, solidifying immunotherapy as a powerful asset for CRC treatment. This review article examines CRC immunotherapies, from their foundation, through emerging avenues for improvement, to future directions.