PAICS (Phosphoribosylaminoimidazole Carboxylase And Phosphoribosylaminoimidazolesuccinocarboxamide Synthase)

Our drug sensitivity analysis further revealed that high-risk patients were more susceptible to gefitinib and erlotinib. These novel findings offer profound insights into potential therapeutic avenues for LUAD patients with poor prognoses, paving the way for future research endeavors. The online version contains supplementary material available at 10.1007/s43657-025-00223-y.

We demonstrate the practical application of this method through a real-world case study of metastatic colorectal cancer, highlighting its utility in enhancing the robustness and credibility of unanchored PAIC results. Our findings emphasise the necessity of formal quantitative sensitivity analysis in interpreting unanchored PAIC results, as it quantifies the robustness of conclusions regarding potential unmeasured confounders and supports more robust, reliable, and informative decision-making in healthcare.

ACADL functions as a mitochondria-associated tumor suppressor that impedes LUAD progression through activation of the FOXO3a/PUMA signaling pathway, underscoring its potential as a therapeutic target for LUAD.

In vivo experiments confirmed its ability to provide prolonged and stable C1QBP inhibition along with enhanced antitumor efficacy. In conclusion, our study suggests that C1QBP may serve as a valuable biomarker for tumour prognosis and that silencing C1QBP using HA gel-siC1QBP -either alone or combined with targeted/ immunotherapies -represents a promising therapeutic strategy against tumors.

Only one PAIC reported TEMs separately from PFs. TEMs and PFs identified herein can help inform future clinical trial design and serve as a primer when conducting PAICs evaluating OS and PFS in ND/RR-MM.

PBRS is a prognostic tool in LUAD, identifying PBRS-high patients who may benefit from immunotherapy or DDR-targeted therapies. PBRS-low patients exhibit sensitivity to metabolic inhibitors. PAICS is a potential therapeutic target.

This study unveils the expression characteristics and biological significance of exosome-associated genes in lung cancer. The differential expression of these genes not only offers potential biomarkers for early diagnosis of lung cancer but also lays a foundation for further research into their biological functions in this disease.

Treating TAMR cells with Decitabine, a demethylating agent, or Farudodstat, a pyrimidine biosynthesis inhibitor, markedly augmented the efficacy of tamoxifen. Restoring ASS1 expression or inhibiting pyrimidine biosynthesis reinstated tamoxifen sensitivity. ASS1 could be a potential biomarker and therapeutic target in tamoxifen-resistant ILC patients, warranting further investigation.

A diagnostic model providing new insight into the molecular mechanisms underlying NSCLC is proposed. However, further experimental verification is required to assess its practical value for NSCLC and other lung cancer subtypes before clinical application.

Subsequently, a series of in vitro and in vivo experiments showed that PPAT, PAICS, GART, ADSL, and ADSS2 are key target genes. Collectively, LEDGF binds H3R17me2a to regulate purine nucleotide metabolism in SETD2 mutant ccRCC cells, promoting tumor proliferation, and may be an effective therapeutic target.

Evaluating the efficacy of these inhibitors for treating different types of cancers, especially leukemia, is recommended. This may be a starting point for the development of new PAICS inhibitors..

Mechanistically, qRT-PCR and western blot analyses suggested that GART deletion could inhibit the activation of the PAICS-Akt-β-catenin pathway in vivo. Our study indicated a tumor-promoting function of GART in LC through the regulation of the PAICS-Akt-β-catenin axis, and it may be used as a therapeutic target for NSCLC.