PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha)

Our findings demonstrate that immune resistance in FLC is mediated by both local T-cell exclusion and exhaustion, with combination CXCR4 and PD-1 blockade acting cooperatively to overcome these independent mechanisms. These results highlight the versatility of the human TSC system to aid in the study of rare cancer types and provide important preclinical evidence for the rational design of combination immunotherapy in FLC, which currently lacks any effective systemic therapy.

P1, N=20, Recruiting, University Hospital Tuebingen | Not yet recruiting --> Recruiting

In vivo experiments demonstrated that AIGG significantly reversed depression-like behaviors in both forced swim and tail suspension tests, suppressed Interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and elevated β-nerve growth factor (β-NGF) levels, attenuated neuroinflammatory infiltration and neuronal apoptosis in brain tissue, and upregulated protein expression of protein kinase cAMP-activated catalytic subunit alpha (PRKACA), brain-derived neurotrophic factor (BDNF), and postsynaptic density protein 95 (PSD95). The study confirmed that AIGG alleviates depression by activating the cAMP-PRKACA-BDNF axis to restore synaptic plasticity, providing a novel natural product-based strategy for treatment of the resistant depression.

Prior molecular studies have focused mainly on the DNAJB1-PRKACA fusion gene, which is pathognomonic for FLC, but no reliable circulating biomarker has been established for FLC diagnosis or disease monitoring...Routine measurement of serum PCT could facilitate earlier recognition of FLC and also provide a non-invasive tool to track treatment response. Future research should validate these findings prospectively, explore the biological mechanisms underlying CALCA overexpression in FLC, and assess whether PCT-guided monitoring can predict prognosis, improve patient outcomes or clinical trial design in this rare malignancy.

The p53 reactivator APR-246 restores sensitivity of p53R273H-expressing cells to LT1-3. Therefore, LT1-3 possesses multifunctional antitumor properties, directly inhibiting tumor cells and enhancing the efficacy of cisplatin, without causing toxicity to normal cells. Combining LT1-3 with cisplatin holds promise as a first-line therapy for lung cancer, while LT1-3 alone may be suitable for maintenance therapy.

The presence of DNAJ-PKAc creates a vulnerability to the combination of glutamine antimetabolite and ICI therapy in FLC.

A defining molecular hallmark is the DNAJB1-PRKACA fusion gene, found in the majority of cases...Treatment options for advanced disease are limited, with some benefit observed from chemotherapy and targeted agents. Recent developments in molecular therapies and immunotherapy offer promise, but further research and clinical trial participation are essential to improve outcomes in this challenging malignancy.

ERBB2, SMAD3, and PRKACA were pointed out as the skin cancer-related genes. In conclusion, the up-regulation of PETN and the activation of CDKN2A were highlighted as the major induced molecular events by sunscreen, which play a role in skin protection.

IOPN exhibits distinct genetic alterations and a unique immune microenvironment. These features not only elucidate the mechanism underlying the relatively favorable prognosis of IOPN and IOPN-derived pancreatic cancers but also offer novel insights into immune regulation strategies for pancreatic cancer.

Furthermore, L-mimosine was found to arrest MCF-7 cells in the S phase of the cell cycle, as analyzed through cell cycle assays. This research highlights L-mimosine's potential as a promising anticancer agent against breast cancer by promoting apoptosis and interfering with cancer cell cycle progression.

NF449 also prevented osteochondral differentiation of human tendon stem cells. These findings identify Gli1+ tendon sheath progenitors with osteochondral differentiation capacity during heterotopic ossification via activation of GNAS/PKA signaling, suggesting PKA as a potentially effective therapeutic target to treat tendon ossification.

RNA sequencing revealed dysregulation of CREB/CREM targets and compensatory pathways, including Rap1 and PI3K/AKT signaling, as well as candidate gene targets of ICER regulation, including the Protein Kinase A catalytic subunit prkacaa. Our findings suggest that a ubiquitin resistant ICER mitigates melanoma progression and represses oncogenic pathways in a brafV600E melanoma context.