Background: Neovascularization plays a crucial pathogenic role in tumor development and vascular endothelial growth factor (VEGF-A) is a key signaling element that drives angiogenesis, thereby facilitating hepatocellular cancer (HCC) growth and metastasis. We aimed to define the relationship between serum VEGF-A levels and clinical outcomes in a cohort of Turkish patients with HCC. Methods: We enrolled and prospectively followed 84 patients with HCC in our study. Serum VEGF-A levels were measured and we assessed the association between VEGF-A levels and clinical features. Results: Forty-eight patients had cirrhosis while 35 patients were noncirrhotic. Serum VEGF-A levels were significantly lower in HCC patients with cirrhosis compared to non-cirrhotic HCC patients (p = 0.03).In terms of viral hepatitis subtype, 36 (%42.8) of patients were hepatitis B virus (HBV) positive and 8 (%9.5) of patients were hepatitis C virus (HCV) positive. Patients with serum VEGF-A levels ≥100 pg/mL had significantly lower OS rates than patients with serum VEGF-A level <100 pg/mL (p = 0.01). The OS rates were 5.8 and 14.2 months, respectively (p = 0.02). The median OS was 7.38 months (95% CI: 5.89-13.79 months). We observed a significant relationship between serum VEGF-A level and tumor size. Patients with tumor size ≤ 5cm had lower VEGF-A levels than patients with VEGF-A levels <5 cm. The VEGF-A levels were 132.7 and 342.1 pg/mL, respectively (p < 0.001). The median follow-up was 32 months. Conclusions: Serum VEGF-A level, a biological marker of angiogenesis, is an independent predictor of survival in patients with HCC. Serum VEGF-A levels may be utilized to predict response to treatment targeting serum VEGF-A in patients with HCC.

Background: Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. Methods: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. Results: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, respectively. Although CFT was recommended to all families, only 117 families (32.3%) agreed to proceed with genetic testing. Among the first-degree relatives who underwent CFT, 70.3% were female, and 108 of 121 (89.3%) were cancer free. Additionally, 42.7%, 36.7%, and 20.6% were offspring, siblings, and parents of the subject, respectively. Our data suggest that CFT was mostly undertaken (104/117, 88.8%) in families with positive findings in high-risk genes. Conclusions: Cascade family testing can be a powerful tool for primary cancer prevention by identifying at-risk family members. It is of utmost importance to implement genetic counseling approaches leading to increased awareness and communication of genetic testing results.

Background: The Child–Turcotte–Pugh score (CTP) is the most commonly used tool to assess hepatic reserve and predict survival in hepatocellular cancer (HCC). The CTP stratification accuracy has been questioned and attempts have been made to improve the objectivity of the system. Serum insulin-like growth factor-1 (IGF-1)-CTP has been proposed to improve CTP prognostic accuracy. We aimed to validate the IGF-CTP score in our patient population. Patients and Methods: A total of 84 diagnosed HCC patients were enrolled prospectively. IGF-CTP scores in addition to CTP scores were calculated. C-index was used to compare the prognostic significance of the two scoring systems and overall survival (OS). Results: Cirrhosis was present in 48 (57.1%) patients, 35 (41.7%) patients were non-cirrhotic, 36 (42.8%) patients were hepatitis B (HBV) positive, and 8 (9.5%) patients were hepatitis C (HCV) positive. Serum IGF-1 levels were significantly lower in cirrhotic compared with non-cirrhotic patients (p=0.04). There was a significant difference in OS rates of patients with serum IGF-1 level < 50 ng/mL and patients with serum IGF-1 levels ≥ 50 ng/mL (p=0.02); the OS rates were 6.5 and 14.8 months, respectively (p=0.02). The median OS of all patients was 7.38 months (95% CI: 5.89– 13.79). The estimated C-index for CTP and IGF-CTP scores was 0.605 (95% CI: 0.538, 0.672) and 0.599 (95% CI: 0.543, 0.655), respectively. The U statistics indicated that the C-indices between two scoring systems are not statistically different (P= 0.91). Conclusion: This study evaluated IGF-1 levels and the IGF-CTP classification in a predominantly HBV (+) cohort of HCC patients with 41.7% non-cirrhotic. Although the prognostic value was similar, among patients with CTP-A, class those reclassified as IGF-CTP B had shorter OS than those with IGF-CTP score A. Thus, further validations of IGF-CTP score in similar populations may add additional value as a stratification tool to predict HCC outcome.

Renal cell carcinoma (RCC) is the most common type of kidney malignancy, and the clear-cell subtype represents the majority of RCCs. RCC is a heterogeneous disease in terms of genetic and histological features which determine the behavior of the disease. The von Hippel–Lindau (VHL) is a tumor suppressor gene and mutations of this gene are seen in 95% of clear-cell RCCs. Inactivation of VHL causes the accumulation of hypoxia-inducible factor-1 (HIF-1), and in turn, accumulation of HIF-1 induces overexpression of vascular endothelial growth factor (VEGF); the increase in VEGF expression makes RCC a highly vascularized tumor, and forms the rationale for antiVEGF treatment. In the past decade, improvement in the survival of RCC patients has been observed due to new effective therapies, such as antiVEGF and mammalian target of rapamycin (mTOR) targeting agents and immune checkpoint inhibitors. The majority of VEGF targeted agents are not just selective to VEGF receptors, but usually also have inhibitory effects on other kinases, such as c-KIT and FLT3. Tivozanib is an extremely potent and selective tyrosine kinase inhibitor (TKI) of VEGFR-1, 2, and 3, with a relatively long half-life, that is approved by the European Commission for the treatment of advanced/metastatic RCC. Tivozanib, at very low serum concentration can inhibit phosphorylation of VEGFR −1, −2, and −3 tyrosine kinase activity. This article summarizes the clinical data on tivozanib in the treatment of advanced/metastatic RCC.

In the era of precision oncology, comprehensive molecular profiling is critical for guiding targeted and immunotherapy strategies. This study presents the analytical and clinical validation of a 1021-gene next-generation sequencing (NGS) panel, designed for use with both formalin-fixed paraffin-embedded (FFPE) tissue- and liquid-biopsy specimens. Analytical validation confirmed the assay’s high sensitivity and specificity across variant types—including SNVs (Single Nucleotide Variations), indels, CNVs (Copy Number Variations), and fusions—down to a 0.5% variant allele frequency. The assay also accurately identified microsatellite instability (MSI) and tumor mutational burden (TMB), essential biomarkers for immunotherapy. Clinical validation was performed on over 1300 solid tumor samples from diverse histologies, revealing actionable alterations in over 50% of cases. The panel detected on-label treatment biomarkers in 12.57% of patients, increasing to 20.15% when immunotherapy markers were included. Additionally, the assay demonstrated strong concordance with orthogonal methods and was effective in detecting variants in plasma-derived circulating tumor DNA in 70% of evaluable cases. These findings support the robust performance and broad clinical applicability of the 1021-gene panel for comprehensive genomic profiling in both tissue and liquid biopsies, offering a valuable tool for personalized cancer treatment.