To what extent stromal cells in the tumor microenvironment are transformed by colorectal cancer (CRC) cells is unexplored.To dissect alterations in these non-malignant cells, researchers performed single-cell multiomics sequencing of 21 patients with microsatellite-stable colorectal cancers and 6 cancer-free, elderly individuals.
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Single-Cell Multiomics Sequencing Reveals Prevalent Genomic Alterations in Tumor Stromal Cells of Human Colorectal Cancer: Cancer Cell. (n.d.). Retrieved October 23, 2020, from https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30489-X?rss=yes&utm_source=dlvr.it&utm_medium=twitter Cite
Researchers indicate p53 as a critical mediator of 5-Fluorouracil (5-FU)-induced cancer stem cell activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for colorectal cancer patients.
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5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation | Nature Communications. (n.d.). Retrieved October 23, 2020, from https://www.nature.com/articles/s41467-020-19173-2 Cite
To what extent stromal cells in the tumor microenvironment (TME) are transformed by colorectal cancer (CRC) cells is unexplored. Researchers performed single-cell multiomics sequencing of 21 patients with microsatellite-stable CRCs and six cancer-free, elderly individuals.
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The authors investigated the variability in HLA class I peptide presentation between different clonal cells of the same colorectal cancer patient, using an organoid system.
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Demmers, L. C., Kretzschmar, K., Van Hoeck, A., Bar-Epraïm, Y. E., van den Toorn, H. W. P., Koomen, M., van Son, G., van Gorp, J., Pronk, A., Smakman, N., Cuppen, E., Clevers, H., Heck, A. J. R., & Wu, W. (2020). Single-cell derived tumor organoids display diversity in HLA class I peptide presentation. Nature Communications, 11(1), 5338. https://doi.org/10.1038/s41467-020-19142-9 Cite
Investigators found in breast tumors that the expression of SMAR1 was decreased in cancer stem cells through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1.
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SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin | Science Signaling. (n.d.). Retrieved October 20, 2020, from https://stke.sciencemag.org/content/13/654/eaay6077 Cite
By RNA sequencing analysis of a pan-cancer cohort comprising >1500 patients and subsequent prediction of protein activity, BCL-XL was identified as the only antiapoptotic BCL-2 protein that was overactivated in colorectal cancer.
[Cell Death & Disease]
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Identification of BCL-XL as highly active survival factor and promising therapeutic target in colorectal cancer | Cell Death & Disease. (n.d.). Retrieved October 19, 2020, from https://www.nature.com/articles/s41419-020-03092-7# Cite
Targovax ASA announced that the colorectal cancer cohort in part 1 of the ONCOS-102 and durvalumab trial in colorectal and platinum-resistant ovarian cancer that has spread to the peritoneum has met the pre-defined efficacy threshold of patients without progression at the end of week 24. The second part of the colorectal expansion cohort is now open for recruitment.
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Investigators evaluated alterations in the colon mucus layer in 2‐, 16‐, and 24‐month‐old mice and aged humans. Aged colons showed defective intestinal mucosal barrier and changed mucus properties. The miR‐124‐3p expression level was significantly increased in the aged distal colonic mucosa, which was accompanied by an increase in pathogens and bacterial translocation. Meanwhile, T‐synthase, the rate‐limiting enzyme in O‐glycosylation, displayed an age‐related decline in protein expression.
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A novel miRNA, miR-1185-1, suppressed the expression of CD24 by targeting its 3’UTR and could be inhibited by SIRT1 via histone deacetylation. Targeting SIRT1 by RNA interference led to elevated H3K9 acetylation on the promoter region of miR-1185-1, which increased expression of miR-1185-1 and further repressed CD24 translation and colorectal cancer stemness.
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SIRT1-mediated expression of CD24 and epigenetic suppression of novel tumor suppressor miR-1185-1 increases colorectal cancer stemness | Cancer Research. (n.d.). Retrieved October 16, 2020, from https://cancerres.aacrjournals.org/content/early/2020/10/10/0008-5472.CAN-19-3188 Cite
Scientists used patient-derived organoids derived from a familial adenomatous polyposis patient to analyze the response to chemotherapeutic agents targeting EGFR, BRAF and MEK.
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Osumi, H., Muroi, A., Sakahara, M., Kawachi, H., Okamoto, T., Natsume, Y., Yamanaka, H., Takano, H., Kusama, D., Shinozaki, E., Ooki, A., Yamaguchi, K., Ueno, M., Takeuchi, K., Noda, T., Nagayama, S., Koshikawa, N., & Yao, R. (2020). Evaluation of the RAS signaling network in response to MEK inhibition using organoids derived from a familial adenomatous polyposis patient. Scientific Reports, 10(1), 17455. https://doi.org/10.1038/s41598-020-74530-x Cite
Artificial modulation of BATF3 was conducted to measure the malignant phenotypes of colorectal cancerc cells, while tumor-bearing mice were examined to determine the in vivo effects.
[Cancer Gene Therapy]
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BATF3 promotes malignant phenotype of colorectal cancer through the S1PR1/p-STAT3/miR-155-3p/WDR82 axis | Cancer Gene Therapy. (n.d.). Retrieved October 15, 2020, from https://www.nature.com/articles/s41417-020-00223-2 Cite