Onco, Volume 3, Issue 3 (September 2023) – 5 articles

Non-small-cell lung cancer (NSCLC) is a heterogeneous group of diseases accounting for 80–85% of lung cancers. A molecular subset of NSCLC (1–2.5%) harboring molecular rearrangements of the tyrosine kinase gene ROS1 is defined as ROS1-positive and is almost exclusively diagnosed in patients with lung adenocarcinoma histology, predominantly nonsmokers. ROS1 is constitutively activated by molecular rearrangements and acts as a main driver of lung carcinogenesis. These findings have provided a strong rationale for the clinical use of tyrosine kinase inhibitors that target ROS1; these inhibitors block ROS1-positive NSCLC and provide clinical benefit. Crizotinib was introduced as a first-line treatment for ROS1-positive NSCLCs, with 75–80% of patients responding and a PFS of about 20 months. More recently developed ROS1-TKIs, such as entrectinib, lorlatinib, taletrectinib, repotrectinib and NVL-520, are active against some resistant ROS1 mutants appearing during crizotinib therapy and more active against brain metastases, frequent in ROS1-positive NSCLC. The development of resistance mechanisms represents a great limitation for the targeted treatment of ROS1-positive NSCLCs with TKIs. Full article

Pancreatic ductal adenocarcinoma is an invasive tumor with similar incidence and mortality rates. Pancreaticoduodenectomy has morbidity and mortality rates of up to 60% and 5%, respectively. The purpose of our study was to assess preoperative features contributing to unfavorable 1-year survival prognosis. Study Design: Retrospective, single-center study evaluating the impact of preoperative features on short-term survival outcomes in head PDAC patients. Forty-four prior features of 172 patients were tested using different supervised machine learning models. Patient records were randomly divided into training and validation sets (80–20%, respectively), and model performance was assessed by area under curve (AUC) and classification accuracy (CA). Additionally, 33 patients were included as an independent revalidation or holdout dataset group. Results: Eleven relevant features were identified: age, sex, Ca-19-9, jaundice, ERCP with biliary stent, neutrophils, lymphocytes, lymphocyte/neutrophil ratio, neoadjuvant treatment, imaging tumor size, and ASA. Tree regression (tree model) and logistic regression (LR) performed better than the other tested models. The tree model had an AUC = 0.92 and CA = 0.85. LR had an AUC = 0.74 and CA = 0.78, allowing the development of a nomogram based on absolute feature significance. The best performance model was the tree model which allows us to have a decision tree to help clinical decisions. Discussion and conclusions: Based only on preoperative data, it was possible to predict 1-year survival (91.5% vs. 78.1% alive and 70.9% vs. 76.6% deceased for the tree model and LR, respectively). These results contribute to informed decision-making in the selection of which patients with PDAC can benefit from pancreatoduodenectomy. A machine learning algorithm was developed for the recognition of unfavorable 1-year survival prognosis in patients with pancreatic ductal adenocarcinoma. This will contribute to the identification of patients who would benefit from pancreatoduodenectomy. In our cohort, the tree regression model had an AUC = 0.92 and CA = 0.85, whereas the logistic regression had an AUC = 0.74 and CA = 0.78. To further inform decision-making, a decision tree based on tree regression was developed. Full article

Background: Various studies have reported associations between frequencies of total peripheral blood lymphocytes and prostate cancer prognosis, but none so far has addressed the prognostic role of CD8+ T-lymphocyte subsets. Methods: A total of 43 prostate cancer patients with metastatic disease and 81 patients with non-metastatic disease were included in this study. Flow cytometry analyses were employed for determining the frequencies of peripheral CD8+ T-lymphocyte subsets. Results: Statistically significant lower levels of terminally differentiated effector (TEMRA) cells in patients with non-metastatic disease vs. patients with metastatic disease were observed. Central memory (CM) and effector memory (EM) CD8+ subsets, were found to be significantly higher in patients with non-metastatic disease vs. patients with metastatic disease. A similar profile was revealed when these CD8+ subsets were analyzed based on the patients’ Gleason scores, as well as by combined disease stage (i.e., non-metastatic vs. metastatic disease) and Gleason score. Conclusions: Peripheral blood-derived CD8+ T-lymphocyte memory subsets could function as biomarkers for the prognosis of PCa. Full article

NUP98 fusions constitute a small subgroup of AML patients and remain a high-risk AML subtype. There are approximately 30 types of NUP98 fusions identified in AML patients. These patients show resistance to currently available therapies and poor clinical outcomes. NUP98 fusions with different fusion partners have oncogenic transformation potential. This review describes how the NUP98 gene acquires oncogenic properties after rearrangement with multiple partners. In the mechanistic part, the formation of nuclear bodies and dysregulation of the HoxA/Meis1 pathway are highlighted. This review also discusses mutational signatures among NUP98 fusions and their significance in leukemogenesis. It also discusses the clinical implications of NUP98 fusions and their associated mutations in AML patients. Furthermore, it highlights therapeutic vulnerabilities in these leukemias that can be exploited as therapeutic strategies. Lastly, this review discusses the gaps in our knowledge regarding NUP98 fusions in AML, as well as future research opportunities. Full article

Esophageal cancer is a formidable challenge in the realm of cancer treatment. Conventional methods such as surgery, chemotherapy, and immunotherapy have demonstrated limited success rates in managing this disease. In response, targeted drug therapies have emerged as a promising strategy to improve outcomes for patients. These therapies aim to disrupt specific pathways involved in the growth and development of esophageal cancer cells. This review explores various drugs used to target specific pathways, including cetuximab and monoclonal antibodies (gefitinib) that target the epidermal growth factor receptor (EGFR), trastuzumab that targets human epidermal growth factor receptor 2 (HER-2), drugs targeting the vascular endothelial growth factor receptor (VEGFR), mTOR inhibitors, and cMET inhibitors. Additionally, the article discusses the impact of drug resistance on the effectiveness of these therapies, highlighting factors such as cancer stem cells, cancer-associated fibroblasts, immune-inflammatory cells, cytokines, hypoxia, and growth factors. While drug targeting approaches do not provide a complete cure for esophageal cancer due to drug resistance and associated side effects, they offer potential for improving patient survival rates. Full article