Onco, Volume 5, Issue 1 (March 2025) – 11 articles

Cancer vaccines offer an exciting option for active immunotherapy, providing a potentially safe and effective treatment that also prevents or minimizes toxic side effects in vaccinated patients. Clinical results from previous phase III clinical trials have suggested that the efficacy of cancer vaccines largely depends on their potential to trigger robust immunological responses. A preexisting immune response to cancer-specific peptides is crucial for achieving a meaningful clinical outcome during vaccinations. However, various factors may hinder the effectiveness of therapeutic vaccines. By overcoming these challenges, cancer vaccines have the potential to become a cornerstone in immunotherapy. This review aims to share our insights on the major challenges that are encountered when optimizing the potential of cancer vaccines, particularly focusing on important aspects regulating their clinical efficacy, such as vaccine composition, the adjuvant to be used and the HLA-restricting element for the tumor peptides targeted by a particular vaccine. Additionally, we discuss several obstacles which hindered the successful clinical development of therapeutic cancer vaccines, such as the standard of care, the clinical design, and the choice of the antigen(s) to be included in vaccine formulation. The identification of patients that are most likely to respond to vaccinations by developing immunological responses and the desirable clinical efficacy are also crucial, and, therefore, predictive biomarkers are strictly required. Finally, we present our views on future prospects that may lead to an enhancement of the anticancer effects of vaccines, ensuring their pivotal role in cancer immunotherapy. Full article

During the last decade, a new therapeutic revolution has involved the management of hepatocellular carcinoma (HCC). This is made possible thanks to the documented efficacy of immunotherapy for this disease. In addition, new evidence has demonstrated the role of the gut–liver axis and gut microbiota in host homeostasis, tumor development, and response to therapies. In particular, intestinal dysbiosis can alter the tumor microenvironment, leading to the activation of intracellular signaling pathways that promote carcinogenesis. The composition of gut microbiota proved to influence the immune checkpoint inhibitors (ICIs) efficacy and drug toxicities. Therefore, this review aims to deepen knowledge about the immunomodulatory role of gut microbiota and its possible employment as diagnostic and predictive biomarkers in diagnosis and response to HCC immunotherapy, respectively. The research was conducted through the analysis of Pubmed and Web of Science (WoS) databases for literature studies on the relationship between gut microbiota and HCC from 2015 to 2025. Full article

Background/Objectives: The accurate prediction of overall survival (OS) in cancer patients is crucial for personalized treatment strategies. Methods: In this study, we developed machine learning models to predict OS by integrating clinical and mutational features from a cohort of 25,508 cancer patients. Key features included tumor mutational burden (TMB), microsatellite instability (MSI), fraction of genome altered (FGA), copy number alterations (CNA), age, sex, race, cancer type, and metastasis status. Results: We applied multiple Random Forest, Gradient Boosting, and Ensemble models, achieving an accuracy of 74% for overall survival status, and a C-Index of 0.76 using the Random Survival Forest model. Importantly, FGA, age, MSI score, TMB, cancer type, and metastasis status were identified as major predictors of OS across all models. We also integrated treatment data from 16,603 patients, demonstrating that therapies like platinum, carboplatin, and taxanes are associated with differences in survival predictions, with some therapeutic regimens showing minimal impact. Conclusions: Our findings highlight the potential of using machine learning to predict OS by incorporating both clinical and mutational features. These models offer a promising approach for improving patient outcomes and could be further validated in prospective studies for clinical use. Full article

Mirtrons represent a new subclass of microRNAs (miRNAs) that are processed through non-canonical biogenesis pathways. Unlike canonical miRNAs, which require Drosha-mediated cleavage, mirtrons are generated via the splicing of short intronic sequences, bypassing Drosha entirely. While mirtrons are found across a variety of organisms, their conservation between species is relatively low. This evolutionary divergence has resulted in mirtrons acquiring species-specific regulatory functions. In humans, mirtrons remain an understudied group of regulatory RNAs. However, emerging evidence highlights their critical roles in cancer biology. These small RNAs influence a range of oncogenic processes, including tumor initiation, progression, metastasis, and resistance to therapy. By directly regulating the expression of oncogenes and tumor suppressor genes, mirtrons serve as key molecular mediators within cellular signaling pathways. What sets mirtrons apart from canonical miRNAs is their unique mode of biogenesis and structural attributes, which reveal alternative regulatory mechanisms that could be exploited in cancer biology. Recent advances in understanding their functions suggest that mirtrons hold significant potential as biomarkers for cancer diagnosis and prognosis. Additionally, their role as modulators of cancer pathways positions them as promising therapeutic targets in precision oncology. This review delves into the growing body of research on mirtrons, focusing on their biogenesis, biological roles, and implications in cancer. By emphasizing their distinct features and clinical relevance, it aims to provide a comprehensive perspective on the potential applications of mirtrons in advancing cancer diagnostics and therapeutics. Full article

Background/Objectives: Treatment options for advanced HCC are limited. Immunotherapy, a promising new therapeutic, has recently been incorporated as a first-line systemic treatment. This study evaluates immunotherapy uptake and disparities in its adoption prior to first-line approval, which are currently unknown. Methods: Patients diagnosed with stage IV HCC between 2014 and 2019 were identified in the National Cancer Database (NCDB). Multivariable logistic regression analysis was performed for demographic and clinical variables to determine their association with the receipt of immunotherapy. Results: A total of 18,248 patients were diagnosed with stage IV HCC, of which 977 (5.35%) received immunotherapy. From 2014 to 2019, the rate of immunotherapy uptake increased each year, with an approximate 25-fold increase overall. On multivariable analysis, patients with a more recent period of diagnosis (OR: 30.19, 95% CI: 16.47–55.33), with private insurance (OR: 2.56, 95% CI: 1.62–4.04), with treatment at an academic or research center (OR: 1.97, 95% CI: 1.37–2.82), or with an income ≥ USD 63,333 (OR: 1.27, 95% CI: 1.01–1.59) were more likely to receive immunotherapy. Conclusions: Various demographic factors impact the receipt of immunotherapy in the pre-approval setting, such as income, insurance status, and treatment center. As immunotherapy use will likely further expand and these disparities may potentially persist following first-line approval, strategies to mitigate them are especially important. Full article

Background/Objectives: Lip cancer represents one of the most prevalent malignant neoplasms in the oral cavity worldwide. This study investigated the prevalence, epidemiological profile, and survival rates of lip squamous cell carcinoma cases at the Liga Norte Riograndense Contra o Câncer (LNRCC) through a 15-year retrospective analysis. Methods: Data collection included sociodemographic characteristics, risk factors, tumor features, staging, and treatment modalities from 348 patient records. Statistical analysis was performed using Stata 12.0 and SPSS 22.0. Results: Results showed a predominance of male patients (70.4%), with a mean age of 65.51 years, mostly brown-skinned, illiterate individuals working in rural areas and residing in the state’s eastern region. Moderately differentiated squamous cell carcinoma (82.8%) affecting the lower lip (89.1%) was most frequent, with a tendency toward advanced staging. The overall survival rate was 88.90%, with lower rates observed among white, illiterate, and substance-using patients, as well as those with advanced-stage disease and chemotherapy treatment. Conclusions: Notably, race emerged as the most significant survival predictor, with white individuals showing consistently lower survival rates regardless of disease characteristics or treatment approach. Full article

Tumor dormancy plays a pivotal role in cancer relapse. Dormant tumor cells have been identified in distant sites, even in early-stage tumors, and are associated with worse outcomes. This review explores the current understanding of the molecular and cellular mechanisms behind tumor dormancy, including the role of the immune system and the microenvironment. Targeting dormant tumor cells could be a therapeutic strategy to offer long-term remission and potentially cure cancer. Unfortunately, the translation of this knowledge in clinical practice is lacking. We assess the feasibility of detecting and measuring dormant tumor cells in clinical practice, and give an overview of potential therapeutic targets, both in terms of maintaining tumor cells in a dormant state, and in terms of eradicating this tumor population. Full article

The integration of small interfering RNA (siRNA) with traditional cancer therapies represents a promising frontier in oncology aimed at enhancing treatment effectiveness, reducing side effects, and overcoming drug resistance. This review highlights the potential of siRNA to selectively silence genes that are overexpressed or uniquely expressed in cancer cells, thereby disrupting critical pathways that support tumor growth and survival. Key target genes discussed include survivin, VEGF, EGFR, c-MET, HER2, MUC1, and Bcl-2, all of which play vital roles in tumor proliferation, angiogenesis, and resistance to therapies. Clinical trials investigating various siRNA candidates, such as EZN-3042 and ALN-VSP, indicate that these therapies are generally well-tolerated; however, significant challenges persist, including the effective delivery and stability of siRNA. Recent advancements in nanoparticle-based delivery systems have shown promise in addressing these issues. Future research will focus on optimizing siRNA delivery methods, personalizing therapies based on individual genetic profiles, and establishing clearer regulatory guidelines for approval. As the field evolves, siRNA-based combination therapies are poised to become an integral part of precision oncology, offering new therapeutic options and hope for patients with difficult-to-treat cancers. Full article

Background/Objectives: Multiple immune-modulatory strategies have been tested in efforts to mitigate the pro-tumor microenvironment in pediatric high-grade glioma. HSV1716 is an oncolytic virus that previously demonstrated evidence of response in adult and pediatric patients. PBTC-037 was a single-center phase I trial developed and performed by the Pediatric Brain Tumor Consortium (PBTC) to estimate the maximum tolerated dose or recommended phase II dose of HSV1716 administered during surgical resection. Methods: Patients aged 12 to 21 years with recurrent or refractory high-grade glioma for whom surgical resection was clinically indicated were eligible. After maximal tumor resection, patients received one intraoperative dose of HSV1716. Results: Two patients were enrolled; one was later deemed ineligible yet was continued in follow up for safety. Both patients underwent complete tumor resection with the administration of HSV1716. Shortly after the enrollment of the two patients, this study was closed to accrual due to a change in the sponsor’s investment focus. One patient completed the 8-week reporting period without toxicity. The second patient who was later deemed ineligible had no evidence of dose-limiting toxicity. The two patients had progressive disease at 1.9 and 2.9 months after enrollment; both eventually died due to progressive disease at 7.5 months. Conclusion: We describe the administration of HSV1716 to two pediatric patients with recurrent high-grade glioma, without evidence of dose-limiting toxicity. Oncolytic viruses are currently being tested in pediatric patients in larger combinatorial trials. Despite the limited numbers, the data presented here will hopefully provide incremental steps toward improved immunovirotherapy of pediatric brain tumors. Full article