Using genome-wide radiogenetic profiling, we functionally dissect vulnerabilities of cancer cells to ionizing radiation (IR). We identify ERCC6L2 as a major determinant of IR response, together with classical DNA damage response genes and members of the recently identified shieldin and CTC1-STN1-TEN1 (CST) complexes. We show that ERCC6L2 contributes to non-homologous end joining (NHEJ), and it may exert this function through interactions with SFPQ. In addition to causing radiosensitivity, ERCC6L2 loss restores DNA end resection and partially rescues homologous recombination (HR) in BRCA1-deficient cells. As a consequence, ERCC6L2 deficiency confers resistance to poly (ADP-ribose) polymerase (PARP) inhibition in tumors deficient for both BRCA1 and p53. Moreover, we show that ERCC6L2 mutations are found in human tumors and correlate with a better overall survival in patients treated with radiotherapy (RT); this finding suggests that ERCC6L2 is a predictive biomarker of RT response.

Despite offering little overall benefit and emerging concerns about their safety, dietary supplements have become increasingly popular. Trust in advertising them may contribute to high confidence in dietary supplements in public opinion. To develop and validate a screening questionnaire intended for the general public regarding knowledge about dietary supplements and a questionnaire on trust in advertising dietary supplements, and to identify the association between these constructs. The development and validation of the measures was overseen by the panels of experts. The conceptual frameworks of the constructs were scientifically well grounded. A set of semi-structured interviews and anonymous web-based surveys was performed. The final questionnaire was applied to 220 non-medically educated people and 121 medically educated people. A 17-item questionnaire on knowledge about dietary supplements and eight-item questionnaire on trust in advertising dietary supplements were developed. The measures presented satisfactory proof of validity, however, the psychometric properties of the questionnaire on knowledge were modest. Both the knowledge about dietary supplements in the study group and trust in advertising them were low. A significant negative relationship was found between knowledge about dietary supplements and trust in advertising them among the general public (Pearson’s r = -0.42, 95%CI: -0.52 to -0.30, p<0.0001). This association was especially pronounced in people who reported not taking dietary supplements (Pearson’s r = -0.61, 95%CI: -0.76 to -0.39, p<0.0001). The extensive advertising of dietary supplements appears to be in conflict with promoting evidence-based knowledge about them, which raises substantial concerns for the public health. The results of the study are only preliminary and require further confirmation and exploration.

Head and neck squamous cell carcinomas (HNSCCs) contribute to over 300,000 deaths every year worldwide. Although the survival rates have improved in some groups of patients, mostly due to new treatment options and the increasing percentage of human papillomavirus (HPV)-related cancers, local recurrences and second primary tumors remain a great challenge for the clinicians. Presently, there is no biomarker for patient surveillance that could help identify patients with HNSCC that are more likely to experience a relapse or early progression, potentially requiring closer follow-up or salvage treatment. MicoRNAs (miRNAs) are non-coding RNA molecules that posttranscriptionally modulate gene expression. They are highly stable and their level can be measured in biofluids including serum, plasma, and saliva, enabling quick results and allowing for repeated analysis during and after the completion of therapy. This has cemented the role of miRNAs as biomarkers with a huge potential in oncology. Since altered miRNA expression was described in HNSCC and many miRNAs play a role in radio- and chemotherapy resistance, cancer progression, and metastasis, they can be utilized as biomarkers of these phenomena. This review outlines recent discoveries in the field of extracellular miRNA-based biomarkers of HNSCC progression and metastasis, with a special focus on HPV-related cancers and radioresistance.

Introduction: Tacrolimus (TAC) metabolism rate has the potential to impact graft function after kidney transplantation (KTx). We aimed to analyze the relationship between the early post-KTx TAC C/D ratio (blood trough concentration normalized by total daily dose) and kidney graft function in a 2-year follow-up. Methods: We retrospectively analyzed data from 101 post-KTx patients at 3, 6, 12, and 24 months after KTx to identify the C/D ratio cutoff value optimal for dividing patients into fast and slow TAC metabolizers. We investigated the relationship between their TAC metabolism rate and graft function. Results: Patients were divided based on the TAC C/D ratio at 6 months after KTx of 1.47 ng/mL * 1 mg. Fast metabolizers (C/D ratio <1.47 ng/mL * 1 mg) presented with significantly worse graft function throughout the whole study period (p < 0.05 at each timepoint) and were significantly less likely to develop good graft function (estimated glomerular filtration rate ≥45 mL/min/1.73 m²) than slow metabolizers. Our model based on donor and recipient age, recipient sex and slow/fast metabolism status allowed for identification of patients with compromised graft function in 2-year follow-up with 66.7% sensitivity and 94.6% specificity. Conclusion: Estimating TAC C/D ratio at 6 months post-KTx might help identify patients at risk of developing deteriorated graft function in a 2-year follow-up.

Introduction: There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the RDW or SII, with the latter combining the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These indices were shown to be prognostic for survival in some malignancies. The purpose of this study was to evaluate the association between pre-treatment RDW and SII, and OS in patients treated with radiotherapy for primary localised cervical cancer. Material and Methods: This retrospective analysis included patients treated with definitive CRT between 2011 and 2017 for histopathologically confirmed FIGO 2018 stage IB2-IVA cervical cancer. Statistical analysis was performed using the Kaplan–Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the AIC serving as a prediction error estimator. Results: The study group included 249 patients with a median age of 57.2 years and a median follow-up of 75.8 months. The majority were diagnosed with squamous cell carcinoma (237; 95.2%) and had FIGO stage III (211; 84.7%). Approximately half of the patients (116; 46.4%) had regional lymph node metastases. Patients with a low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS (p = 0.001 and p = 0.002). The RDW remained as an independent prognostic factor in the multivariable model (high vs. low; HR = 2.04; 95% CI: 1.32–3.16; p = 0.001). Including RDW in the model decreased the Akaike Information Criterion from 1028.25 to 1018.15. Conclusions: The RDW is a cheap and widely available index that is simultaneously an independent prognostic factor for survival and could be used to improve pre-treatment prognosis assessments in patients with cervical cancer undergoing CRT. Available data encourage assessing the RDW as a prognostic factor in prospective trials to aid the identification of candidates for treatment escalation.

53BP1 nucleates the anti-end resection machinery at DNA double-strand breaks, thereby countering BRCA1 activity. Loss of 53BP1 leads to DNA end processing and homologous recombination in BRCA1-deficient cells. Consequently, BRCA1-mutant tumors, typically sensitive to PARP inhibitors (PARPi), become resistant in the absence of 53BP1. Here, we demonstrate that the ‘leaky’ DNA end resection in the absence of 53BP1 results in increased micronuclei and cytoplasmic double-stranded DNA, leading to activation of the cGAS-STING pathway and pro-inflammatory signaling. This enhances CD8⁺ T cell infiltration, activates macrophages and natural killer cells, and impedes tumor growth. Loss of 53BP1 correlates with a response to immune checkpoint blockade (ICB) and improved overall survival. Immunohistochemical assessment of 53BP1 in two malignancies, high grade serous ovarian cancer and pancreatic ductal adenocarcinoma, which are refractory to ICBs, reveals that lower 53BP1 levels correlate with an increased adaptive and innate immune response. Finally, BRCA1-deficient tumors that develop resistance to PARPi due to the loss of 53BP1 are susceptible to ICB. Therefore, we conclude that 53BP1 is critical for tumor immunogenicity and underpins the response to ICB. Our results support including 53BP1 expression as an exploratory biomarker in ICB trials for malignancies typically refractory to immunotherapy.