Mutant KRAS Triggers Functional Reprogramming of Tumor-Associated Macrophages in Colorectal Cancer

Mutationally activated KRAS in tumor cells reprograms macrophages to a tumor-associated macrophage-like phenotype via a combination effect of tumor-derived CSF2 and lactate.
[Signal Transduction and Targeted Therapy]
Liu, H., Liang, Z., Zhou, C., Zeng, Z., Wang, F., Hu, T., He, X., Wu, X., Wu, X., & Lan, P. (2021). Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer. Signal Transduction and Targeted Therapy, 6(1), 1–13. https://doi.org/10.1038/s41392-021-00534-2 Cite
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Mutant KRAS Drives Metabolic Reprogramming and Autophagic Flux in Premalignant Pancreatic Cells

The authors report dynamic metabolic reprogramming in immortalized human non-cancerous pancreatic ductal epithelial cells.
[Cancer Gene Therapy]
Suzuki, T., Kishikawa, T., Sato, T., Takeda, N., Sugiura, Y., Seimiya, T., Sekiba, K., Ohno, M., Iwata, T., Ishibashi, R., Otsuka, M., & Koike, K. (2021). Mutant KRAS drives metabolic reprogramming and autophagic flux in premalignant pancreatic cells. Cancer Gene Therapy, 1–14. https://doi.org/10.1038/s41417-021-00326-4 Cite
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KRAS Mutant Rectal Cancer Cells Interact with Surrounding Fibroblasts to Deplete the Extracellular Matrix

Scientists found that KRAS‐mutant tumors displayed lower expression of genes related to the tumor stroma and remodeling of the extracellular matrix.
[Molecular Oncology]
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Quantifying Single-Cell ERK Dynamics in Colorectal Cancer Organoids Reveals EGFR as an Amplifier of Oncogenic MAPK Pathway Signaling

To elucidate the interplay between epidermal growth factor signaling and extracellular-regulated kinase activation in tumors, scientists used patient-derived organoids from KRAS and BRAF mutant colorectal cancer.
[Nature Cell Biology]
Ponsioen, B., Post, J. B., Buissant des Amorie, J. R., Laskaris, D., van Ineveld, R. L., Kersten, S., Bertotti, A., Sassi, F., Sipieter, F., Cappe, B., Mertens, S., Verlaan-Klink, I., Boj, S. F., Vries, R. G. J., Rehmann, H., Vandenabeele, P., Riquet, F. B., Trusolino, L., Bos, J. L., & Snippert, H. J. G. (2021). Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-021-00654-5 Cite
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SWATH-MS Proteomics of PANC-1 and MIA PaCa-2 Pancreatic Cancer Cells Allows Identification of Drug Targets Alternative to MEK and PI3K Inhibition

Scientists compared PANC-1 and MIA PaCa-2 pancreatic cancer cells which are, respectively, resistant and sensitive to MEK- and PI3K-targeted therapy.
[Biochemical and Biophysical Research Communications]
Aguilar-Valdés, A., Noriega, L. G., Tovar, A. R., Ibarra-Sánchez, M. de J., Sosa-Hernández, V. A., Maravillas-Montero, J. L., & Martínez-Aguilar, J. (2021). SWATH-MS proteomics of PANC-1 and MIA PaCa-2 pancreatic cancer cells allows identification of drug targets alternative to MEK and PI3K inhibition. Biochemical and Biophysical Research Communications, 552, 23–29. https://doi.org/10.1016/j.bbrc.2021.03.018 Cite
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Clinical Significance of RAS Pathway Alterations in Pediatric Acute Myeloid Leukemia

Scientists analyzed the frequency, clinical significance, and prognostic relevance of RAS pathway alterations in 328 pediatric patients with de novo acute myeloid leukemia.
[Haematologica]
Kaburagi, T., Yamato, G., Shiba, N., Yoshida, K., Hara, Y., Tabuchi, K., Shiraishi, Y., Ohki, K., Sotomatsu, M., Arakawa, H., Matsuo, H., Shimada, A., Taki, T., Kiyokawa, N., Tomizawa, D., Horibe, K., Miyano, S., Taga, T., Adachi, S., … Hayashi, Y. (2020). Clinical significance of RAS pathway alterations in pediatric acute myeloid leukemia. Haematologica. https://doi.org/10.3324/haematol.2020.269431 Cite
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The Noncoding RNAs SNORD50A and SNORD50B-Mediated TRIM21-GMPS Interaction Promotes the Growth of p53 Wild-Type Breast Cancers by Degrading p53

Functional studies showed that SNORD50A and SNORD50B deletions strongly inhibited the proliferation, migration, invasion and tumorigenic potential, and induced cell cycle arrest and apoptosis in p53 wild-type breast cancer cells, while exerted the opposite effects in p53 mutated breast cancer cells.
[Cell Death & Differentiation]
Su, X., Feng, C., Wang, S., Shi, L., Gu, Q., Zhang, H., Lan, X., Zhao, Y., Qiang, W., Ji, M., & Hou, P. (2021). The noncoding RNAs SNORD50A and SNORD50B-mediated TRIM21-GMPS interaction promotes the growth of p53 wild-type breast cancers by degrading p53. Cell Death & Differentiation, 1–15. https://doi.org/10.1038/s41418-021-00762-7 Cite
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SOX9 Modulates Cancer Biomarker and Cilia Genes in Pancreatic Cancer

To identify genes regulated by SOX9, scientists performed siRNA knockdown of SOX9 followed by RNA-seq in PANC-1 cells, a human PDAC cell line.
[Human Molecular Genetics]
Edelman, H. E., McClymont, S. A., Tucker, T. R., Pineda, S., Beer, R. L., McCallion, A. S., & Parsons, M. J. (2021). SOX9 modulates cancer biomarker and cilia genes in pancreatic cancer. Human Molecular Genetics, ddab064. https://doi.org/10.1093/hmg/ddab064 Cite
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Signaling Pathways in Intestinal Homeostasis and Colorectal Cancer: KRAS at Centre Stage

Scientists summarize the signaling pathways contributing to intestinal cell fates and homeostasis functions, focusing on intestinal stem cell proliferation, cell junction formation, remodeling, hypoxia, the impact of intestinal microbiota, the immune system, inflammation, and metabolism.
[Cell Communication and Signaling]
Ternet, C., & Kiel, C. (2021). Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage. Cell Communication and Signaling, 19(1), 31. https://doi.org/10.1186/s12964-021-00712-3 Cite
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Activation of the MAPK Pathway Mediates Resistance to PI3K Inhibitors in Chronic Lymphocytic Leukemia (CLL)

Researchers present findings from longitudinal whole-exome sequencing of multiply relapsed CLL patients enrolled in phosphatidylinositol 3-kinase delta (PI3Ki) trials. The non-responder subgroup was characterized by baseline activating mutations in MAP2K1, BRAF and KRAS in 60% of patients.
[Blood]
Murali, I., Kasar, S., Naeem, A., Tyekucheva, S., Ph. D., Khalsa, J. K., Thrash, E. M., Itchaki, G., Livitz, D., Leshchiner, I., Ph. D., Dong, S., Fernandes, S. M., Getz, G., Johnson, A., Ph. D., & Brown, J. R. (2021). Activation of the MAPK pathway mediates resistance to PI3K inhibitors in chronic lymphocytic leukemia (cll). Blood, blood.2020006765. https://doi.org/10.1182/blood.2020006765 Cite
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Immune Stimulating Antibody‐Photosensitizer Conjugates via Fc‐Mediated Dendritic Cell Phagocytosis and Phototriggered Immunogenic Cell Death for KRAS‐Mutated Pancreatic Cancer Treatment

Cetuximab‐conjugated maleimide‐polyethylene glycol‐chlorin e6 (CMPC) was designed to strengthen its antitumor efficacy. With strong affinity for epidermal growth factor receptor overexpressing Aspc‐1 cells, CMPC with laser exerted the greatest cytotoxicity and induction of immunogenic cell death.
[Small]
Immune Stimulating Antibody‐Photosensitizer Conjugates via Fc‐Mediated Dendritic Cell Phagocytosis and Phototriggered Immunogenic Cell Death for KRAS‐Mutated Pancreatic Cancer Treatment - Kim - - Small - Wiley Online Library. (n.d.). Retrieved February 23, 2021, from https://onlinelibrary.wiley.com/doi/10.1002/smll.202006650 Cite
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