Environmental and occupational exposures have been associated with an increased risk of different types of cancers, although the exact mechanisms of higher carcinogenesis risk are not always well understood. Lung cancer is the leading cause of global cancer mortality, and, also, genitourinary neoplasms are among the main causes of cancer-related deaths in Western countries. The purpose of this review is to describe the main environmental and occupational factors that increase the risk of developing lung and genitourinary cancers and to investigate carcinogenesis mechanisms that link these agents to cancer onset. Further objectives are to identify methods for the prevention or the early detection of carcinogenic agents and, therefore, to reduce the risk of developing these cancers or to detect them at earlier stages.

Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC. To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments. A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC. From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel. Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients. Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials.

Background: KRAS mutation‐positive (KRAS‐positive), advanced nonsmall‐cell lung cancer (NSCLC) is characterized by a poor prognosis. KRAS mutations are extremely heterogeneous from a biologic point of view, and real‐world data by mutation subtype in the era of immunotherapy are still incomplete.Methods: The objective of this study was to retrospectively analyze all consecutive patients with advanced/metastatic, KRAS‐positive NSCLC who were diagnosed at a single academic institution since the advent of immunotherapy. The authors report on the natural history of the disease as well as the efficacy of first‐line treatments in the entire cohort and by KRAS mutation subtypes as well as the presence/absence of co‐mutations.Results: From March 2016 to December 2021, the authors identified 199 consecutive patients who had KRAS‐positive, advanced or metastatic NSCLC. The median overall survival (OS) was 10.7 months (95% confidence interval [CI], 8.5–12.9 months), and there were no differences by mutation subtype. Among 134 patients who received first‐line treatment, the median OS was 12.2 months (95% CI, 8.3–16.1 months), and the median progression‐free survival was 5.6 months (95% CI, 4.5–6.6 months). At multivariate analysis, only an Eastern Cooperative Oncology Group performance status of 2 was associated with significantly shorter progression‐free survival and OS.Conclusions: KRAS‐positive, advanced NSCLC is characterized by a poor prognosis despite the introduction of immunotherapy. Survival was not associated with KRAS mutation subtype.Plain Language Summary: This study evaluated the efficacy of systemic therapies for advanced/metastatic nonsmall cell lung cancer harboring KRAS mutations, along with the potential predictive and prognostic role of mutation subtypes. The authors found that advanced/metastatic, KRAS‐positive nonsmall cell lung cancer is characterized by a poor prognosis and that first‐line treatment efficacy is not related to different KRAS mutations, although a numerically shorter median progression‐free survival was observed in patients who had p.G12D and p.G12A mutations. These results underline the need for novel treatment options in this population, such as next‐generation KRAS inhibitors, which are in clinical and preclinical development.

Background: Immune checkpoint inhibitors (ICIs) represent one of the most effective treatments for patients with cancer. As their activity relies on host immune system reactivity, the role of concomitant medications such as corticosteroids and antibiotics has been extensively evaluated. Preclinical data suggest that opioids may influence the immune system. Methods: a systematic literature revision was performed using specific keywords on the major search engines. Two authors analysed all the studies and provided a selection of the following inclusion and exclusion criteria, respectively: 1. data collection of patients older than 18 years old affected by solid tumours; 2. description of ICIs efficacy in terms of PFS, OS, TTF, and ORR; 3. concomitant ICIs-opioids treatment and 1. language different from English; 2. not pertinent analyses. Results: 523 studies were analysed, and 13 were selected and included in our series. A possible negative interaction between oral opioids and ICIs efficacy was observed. Most evidence was retrospective, and studies were heterogeneous. Conclusions: Even if oral opioids seem to impact negatively on ICIs efficacy in cancer patients, to date there is not sufficient evidence to avoid their prescription in this population.

The clinical management of small cell lung cancer (SCLC) treatment remains a major challenge for thoracic oncologists, with very few therapeutic advances significantly impacting patients’ survival. The recent introduction of immunotherapy in the clinical setting produced a marginal benefit for a limited subset of metastatic patients, while the therapeutic scenario for relapsing extended-disease small cell lung cancers (ED-SCLCs) remains almost deserted. Recent efforts clarified the molecular features of this disease, leading to the identification of key signalling pathways which may serve as potential targets for clinical use. Despite the large number of molecules tested and the numerous therapeutic failures, some targeted therapies have recently shown interesting preliminary results. In this review, we describe the main molecular pathways involved in SCLC development/progression and provide an updated summary of the targeted therapies currently under investigation in SCLC patients.

Lung cancer represent the leading cause of cancer mortality, so several efforts have been focused on the development of a screening program. To address the issue of high overdiagnosis and false positive rates associated to LDCT-based screening, there is a need for new diagnostic biomarkers, with liquid biopsy ncRNAs detection emerging as a promising approach. In this scenario, this work provides an updated summary of the literature evidence about the role of non-coding RNAs in lung cancer screening. A literature search on PubMed was performed including studies which investigated liquid biopsy non-coding RNAs biomarker lung cancer patients and a control cohort. Micro RNAs were the most widely studied biomarkers in this setting but some preliminary evidence was found also for other non-coding RNAs, suggesting that a multi-biomarker based liquid biopsy approach could enhance their efficacy in the screening context. However, further studies are needed in order to optimize detection techniques as well as diagnostic accuracy before introducing novel biomarkers in the early diagnosis setting.