Genomic scarring score predicts the response to PARP inhibitors in non-small cell lung cancer.

PARP inhibitors (PARPi) have shown efficacy in tumours harbouring mutations in homologous recombination repair (HRR) genes. Somatic HRR mutations have been described in patients with Non-Small Cell Lung Cancer (NSCLC), but PARP inhibitors (PARPi) are not yet a therapeutic option. Here we assessed the homologous recombination status of early-stage NSCLC and explored the therapeutic benefit of PARPi in preclinical models.

LKB1 Loss Correlates with STING Loss and, in Cooperation with β-Catenin Membranous Loss, Indicates Poor Prognosis in Patients with Operable Non-Small Cell Lung Cancer.

To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRβ, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (β-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAF mutations were evaluated by Sanger sequencing.

Prognostic Value of Mutations in Colorectal Cancer Patients.

Colorectal cancer (CRC) remains a major public health issue. The detection of parameters that affect CRC prognosis is of great significance. mutations, play a crucial role in tumorigenesis with a strong predictive value.

Generation of Non-Small Cell Lung Cancer Patient-Derived Xenografts to Study Intratumor Heterogeneity.

Recent advances in sequencing technologies have allowed the in-depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreciated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early-stage operable non-small cell lung cancer, we used tumor growth in patient-derived xenograft (PDX) models in mice as a fast-forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency.

Reporting on the Role of miRNAs and Affected Pathways on the Molecular Backbone of Ovarian Insufficiency: A Systematic Review and Critical Analysis Mapping of Future Research.

Ovarian insufficiency is identified as a perplexing entity in the long list of pathologies impairing fertility dynamics. The three distinct classifications of ovarian insufficiency are poor ovarian response, premature ovarian insufficiency/failure, and advanced maternal age, sharing the common denominator of deteriorated ovarian reserve. Despite efforts to define clear lines among the three, the vast heterogeneity and overlap of clinical characteristics renders their diagnosis and management challenging.