AGK (Acylglycerol Kinase)

Knockdown of SCAMP1 expression reduced tumor cell growth, invasion, epithelial‑mesenchymal transition (EMT), and improved sensitivity to 5-fluorouracil (5-FU) in vitro and inhibited tumor cell xenograft growth in nude mice...The data from the current study demonstrated an oncogenic SCAMP1 activity in PDAC. Further study will investigate SCAMP1 as a tumor biomarker and novel target in control of PDAC clinically.

Furthermore, mediation analysis identified potential association pathways involving tumor-resident microbes, LM-related gene signatures, and antitumor immune cells. Overall, this study advanced the understanding of the relationship between LM patterns and LUSC tumor biology, as well as its potential clinical implications, which might advance the tailored management of LUSC.

This case underscores the need for personalized approaches in treating AM, especially those with rare molecular alterations like AGK-BRAF fusion. Insights from genomic and immune profiling may inform future therapeutic strategies to overcome resistance and improve outcomes in this challenging melanoma subtype.

In NF1-LOF tumor cells treated with tovorafenib, increase in phosphorylated-ERK (pERK) was observed at low concentrations, with inhibition of pERK at higher concentrations. When tovorafenib was combined with pimasertib in vitro, synergy was observed in a NF1-LOF embryonal rhabdomyosarcoma PDX model ex vivo and a NF1-LOF MPNST cell line in vitro, suggesting that vertical pathway inhibition is needed in the NF1-LOF mutant setting.

Here, a novel in vivo bioengineered miR-7 molecule, namely BioRNA/miR-7, was used to effectively control target gene expression and NSCLC cell metabolism. Furthermore, BioRNA/miR-7 was demonstrated to remarkably improve pemetrexed antitumor activity in NSCLC patient-derived tumor mice, supporting the role of miR-7 in NSCLC metabolism and potential for BioRNA/miR-7 to improve NSCLC therapy.

Our findings define a critical role of AGK in maintaining the macrophage mitochondrial homeostasis that is associated with mtDNA release and following cGAS-STING activation and type I IFN pathway. Targeting AGK in TAMs may represent a novel strategy to enhance anti-tumoral activity.

Both in vivo and in vitro studies indicated that Netupitant could inhibit the activation of the PI3K/AKT/mTOR signaling pathway. By targeting AGK, Netupitant inhibits its kinase activity, which leads to reduced phosphorylation levels of PTEN, thereby suppressing the activation of the PI3K/AKT/mTOR signaling pathway and ultimately resulting in apoptosis in breast cancer cells.

The detection of BRAF fusions and their many partners was enabled by the Afirma XA exome-enriched RNASeq panel. Although BRAF fusions occurred in only 0.2% of thyroid nodules, they were GSC-Suspicious and lacked typical BRAF/RAS mutations. Interestingly, expression signatures associated with malignancy varied by fusion partner.

Almost half of the cases had nodal metastasis and a third of them showed simultaneous involvement by tumors with discordant molecular drivers. The results highlight the clinical importance of identifying such cases, given the potentially different treatments.

Finally, we revealed that GLUT1 or AGK maintained anti-apoptosis ability in CD8+ T cells via activation of the PI3K/Akt pathway. This finding might identify a therapeutic strategy for advanced HCC.

This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.