Cancers

Background/Objectives: MEK inhibitors (selumetinib, mirdametinib) are the only approved class of targeted therapy for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN), producing partial responses in a substantial proportion of patients (up to 63.6% in adults; objective response rate 19.7% versus 5.4% with placebo in the KOMET trial). Responses, however, are rarely complete or durable, and in malignant peripheral nerve sheath tumor (MPNST) single-agent MEK inhibition is clinically ineffective. Mechanisms of escape from MEK inhibition in these tumors remain poorly characterized and are reported in the literature as isolated primary studies without an integrative analysis. The aim of this review was to systematize both the established molecular mechanisms of resistance to MEK inhibitors in PN and MPNST and the biologically plausible candidate mechanisms extrapolated from other RAS-driven malignancies. Methods: This is a narrative review. A structured search was performed in PubMed, PubMed Central, NCBI Bookshelf, and Scopus, supplemented by clinical practice guidelines and regulatory documents; it covered publications up to 31 May 2026 and was updated in August 2026. Ninety-six sources are cited, and their composition by publication type is reported; record counts at the intermediate screening steps were not maintained, and no PRISMA flow diagram is presented. Results: Mechanisms were classified within a convergent framework into six categories: reactivation of MAPK signaling within the cascade; parallel (bypass) reactivation through receptor tyrosine kinases and adjacent inputs; epigenetic and transcriptional rewiring; cell survival programs; the tumor microenvironment and immune evasion; and intratumoural heterogeneity. Each mechanism was then graded along two independent axes—the strength of evidence that it confers resistance in PN or MPNST (E1–E3) and its therapeutic tractability (T1–T3)—and annotated with the entity and model constituting its evidence source. Conclusions: Resistance to MEK inhibition in PN and MPNST is convergent rather than mechanism-unique. The principal limitation of the field is the near-absence of clinical resistance data from patients progressing on MEK inhibitors; prospective molecular monitoring, rational combination trials, and mechanism-stratifying biomarkers are the priorities.

Oral lichen planus (OLP) is a chronic, immune-mediated inflammatory disorder of the oral mucosa recognized as an oral potentially malignant disorder, with a pooled malignant transformation rate of approximately 1–1.4% that is highest in atrophic-erosive and tongue lesions. Its most feared outcome, oral squamous cell carcinoma (OSCC), remains associated with a 5-year survival below 50% and a substantial clinical, functional, and economic burden. Because conventional management, like topical corticosteroids for OLP and surgery with or without radiotherapy for OSCC, entails cumulative toxicity and limited long-term efficacy, non-pharmacological strategies are attracting growing interest. This narrative review critically appraises the available evidence across the OLP-to-OSCC continuum, examining high-power ablative lasers, low-level laser therapy/photobiomodulation, photodynamic therapy, nutraceutical and phytotherapeutic agents (including melatonin, curcumin, aloe vera, coconut, zinc, and vitamin D), cryotherapy, ozone therapy, probiotics, and psychological interventions, alongside supportive measures in OSCC such as oral hygiene management, photobiomodulation for treatment-related toxicity, and post-treatment rehabilitation. Evidence is strongest and most consistent for photobiomodulation in OLP, whereas most other modalities remain promising but limited by small samples, heterogeneous protocols, and scarce placebo-controlled data. A multidisciplinary, evidence-graded approach is essential to optimize early detection, disease control, and quality of life.

Background: Artificial intelligence-derived parameters hold substantial promise as indicators for tumor prognosis prediction and treatment guidance. However, existing studies have not sufficiently addressed the application of these parameters across different cancer types. Methods: We employed a deep learning algorithm to conduct a multi-cancer analysis for disease-free survival (MC-DFS) prediction using 8856 cases with associated whole-slide images and clinical data. The training cohort consisted of 7392 cases from the TCGA set (24 cancer types), and the independent external validation cohort comprised 1464 cases from the CPTAC and General Hospital sets (9 cancer types). A nomogram prediction signature for disease-free survival (NOMO) was developed by integrating the MC-DFS, tumor stage, and patient age. The prognostic model’s performance was validated in an independent cohort. Results: In the training and validation cohorts, the MC-DFS model achieved area under the curve (AUC) values of 0.750 and 0.682, respectively. It effectively differentiated patients with poorer disease-free survival, with hazard ratios of 4.823 (95% CI: 4.343–5.356, p < 0.0001) in the training cohort and 2.092 (95% CI: 1.472–2.971, p < 0.0001) in the validation cohort. Each cancer subtype’s analysis confirmed the model’s robust performance. Additionally, using nomogram analysis, we developed a multi-model prediction signature for disease-free survival across multiple cancer types based on MC-DFS and the clinicopathologic features in the training cohort. This enhanced model offers more precise risk stratification for stage I malignancies and complements the existing tumor staging systems by identifying high-risk patients. Conclusions: The newly developed MC-DFS shows marked improvements in prognostic predictions across multiple cancer types. With further validations across multiple centers, this nomogram prediction system could become a valuable practical tool for managing various cancers.

Background/Objectives: Cachexia is a multifactorial muscle wasting syndrome driven by inflammation, causing increased catabolism and decreased food intake. Using appetite stimulation as part of multidisciplinary rehabilitation for cachexia is an emerging strategy. Olanzapine was originally developed as an atypical antipsychotic and has since emerged in rehabilitative strategies in patients with brain injury and chemotherapy-induced nausea. In 2023, the American Society of Clinical Oncology (ASCO) issued a rapid recommendation for the use of low-dose (2.5–5 mg) olanzapine to improve appetite and weight in adults with advanced cancer cachexia, based on novel evidence of increased appetite and weight gain. Methods: We retrospectively evaluated the impact of olanzapine on a real-world cohort of 45 patients with appetite concerns undergoing cancer-related rehabilitation. Patients were retrospectively evaluated for changes in body composition metrics and physical therapy (PT) related outcomes. Results: While treatment groups were well matched at baseline, there were no statistical differences between group outcomes, including weight gain, contrary to findings in other populations. However, fatigue was a significant predictor of PT goal completion across the cohort (p = 0.017), highlighting the need for future studies to investigate this relationship more deeply. Conclusions: These results indicate that the effects of olanzapine may vary between different clinical populations and suggest that further investigation into adjuvant therapies remains critical for optimizing care for cancer patients with anorexia.

Background and Objectives: Visceral pleural invasion (VPI) up-classifies non-small cell lung cancer (NSCLC) tumors measuring ≤3 cm from T1 to T2; however, whether this stage migration translates into worse survival in pathologically node-negative disease remains uncertain. This study evaluated the prognostic impact of VPI on overall survival (OS) and progression-free survival (PFS) in this selected population. Materials and Methods: This retrospective single-center cohort study included patients who underwent surgical resection for pathologically node-negative NSCLC with tumors ≤ 3 cm between 2015 and 2021. In the primary analysis, patients with PL0 were compared with those with PL1–PL2, whereas PL3 cases were excluded from the primary comparison and evaluated only in exploratory analyses. Survival outcomes were assessed using Kaplan–Meier analysis and univariable and multivariable Cox regression models. Results: A total of 241 patients were included in the overall cohort (PL0, n = 179; PL1, n = 48; PL2, n = 9; PL3, n = 5). After exclusion of PL3 from the primary analysis, 236 patients remained, including 179 with PL0 and 57 with PL1–PL2. During follow-up, 58 deaths and 81 PFS events occurred in the primary analytic cohort. Kaplan–Meier analysis showed no significant differences between PL0 and PL1–PL2 in OS (log-rank p = 0.655) or PFS (log-rank p = 0.904). In multivariable analysis, VPI was not independently associated with OS (HR 0.785, 95% CI 0.389–1.582; p = 0.498) or PFS (HR 0.908, 95% CI 0.507–1.624; p = 0.744). Increasing age was independently associated with worse OS and PFS, whereas male sex and pneumonectomy were independently associated with worse OS. Conclusions: In surgically treated patients with pathologically node-negative NSCLC and tumors ≤ 3 cm, VPI defined as PL1–PL2 was not independently associated with OS or PFS. These findings suggest that the prognostic implications of VPI-driven up-classification may be context-dependent and should be interpreted together with other clinicopathological factors.