Search Results (120)

Background/Objectives: Mucinous ovarian carcinoma (MOC) is a rare and biologically distinct subtype of epithelial ovarian cancer, typically presenting at an early stage in younger women. Unlike high-grade serous carcinoma, MOC is characterized by unique molecular features—including frequent KRAS mutations and HER2 amplifications—and exhibits limited sensitivity to platinum-based chemotherapy. These differences highlight the need for individualized treatment strategies guided by molecular and histological profiling. This review aims to integrate current evidence on the clinical management of MOC with emerging insights into its molecular biology, with a focus on how these factors influence surgical decision-making, fertility preservation, and adjuvant therapy selection. Methods: We performed a comprehensive narrative review of the literature, synthesizing findings from retrospective cohorts, molecular studies, and clinical guidelines relevant to the surgical, reproductive, and therapeutic management of MOC. Results: Histologic subtype—expansile versus infiltrative—plays a critical role in guiding lymphadenectomy as lymph node metastases are rare (<1%) in expansile tumors but occur in up to 23% of infiltrative cases. Complete surgical staging remains essential for accurate prognostication, yet tailored approaches may reduce overtreatment in low-risk patients. Fertility-sparing surgery (FSS) appears safe in FIGO stage IA expansile MOC, with favorable reproductive outcomes, while higher-stage or infiltrative cases warrant caution. Given MOC’s chemoresistance, the role of adjuvant therapy in early-stage disease remains debated. Targeted strategies, including MEK inhibitors and HER2-directed therapies, are under investigation and may benefit selected molecular subgroups. Conclusions: MOC requires a nuanced, biomarker-informed approach. This review advocates for personalized, evidence-based management supported by multidisciplinary evaluation while underscoring the urgent need for prospective studies and biomarker-driven clinical trials. Full article

Background/Objectives: Urothelial carcinoma (UC) treatment has been transformed by immunotherapy and antibody-drug conjugates (ADCs). This review evaluates the current evidence for these approaches and identifies future directions. Methods: We conducted a structured review of clinical trials, meta-analyses, and guidelines published until early 2025. Results: Immune checkpoint inhibitors have established benefits across multiple settings: post-platinum therapy (pembrolizumab, nivolumab), maintenance therapy (avelumab), adjuvant settings for high-risk muscle-invasive disease (nivolumab), and BCG-unresponsive non-muscle-invasive disease (pembrolizumab). Enfortumab vedotin (targeting Nectin-4) has proven effective in post-platinum/post-immunotherapy. Most significantly, enfortumab vedotin plus pembrolizumab has redefined first-line treatment with unprecedented survival benefits (median OS 31.5 months vs. 16.1 months with chemotherapy; HR 0.47), and nivolumab plus gemcitabine-cisplatin improved outcomes in cisplatin-eligible patients. Key challenges include managing unique toxicity profiles, optimizing treatment sequencing, and developing reliable biomarkers. Conclusions: Combination approaches offer the most promising path forward, with future research needed on resistance mechanisms, biomarker development, and expanding these therapies to earlier disease stages. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype requiring further knowledge of biomarkers to improve targeted therapy. A major resistance mechanism involves breast cancer stem cells (BCSCs) evading the immune system. Neoadjuvant or adjuvant chemotherapy may alter BCSCs and the patients’ immune response. We conducted a retrospective study including 29 early-stage TNBC patients resistant to chemotherapy diagnosed at the Catalan Institute of Oncology (Girona, Spain) in 2010–2019. We obtained 44 paired tumor samples (pre- and post-chemotherapy) from the Tumor Biobank, assessing BCSC biomarkers (CD44, CD24, and ALDH1), PD-L1, and percentages of stromal tumor-infiltrating lymphocytes (TILs). Clinicopathological characteristics were also collected. At baseline, 68% of tumors had high CD44 expression, 55% showed low CD24 expression, 9% had high ALDH1 expression, 91% were PD-L1-negative (<1%), and 64% had a low percentage of stromal TILs. PD-L1 expression significantly increased post-chemotherapy, with 50% of initially negative tumors becoming PD-L1 positive (≥1%) (p = 0.006). No significant changes were observed in BCSC markers or TILs. No association was found between baseline BCSCs and increased PD-L1 expression post-chemotherapy. At a median follow-up of 58.9 months, 48.3% of patients were alive, with non-significant favorable trends in time to progression, disease-free survival, and overall survival in the PD-L1 positivization cohort post-chemotherapy. In conclusion, high-risk early-stage TNBC tumors increased PD-L1 expression after chemotherapy, potentially affecting clinical outcomes. BCSCs remained stable and independent of the tumor immunogenicity post-chemotherapy. Further studies are needed to explore the relationship between BCSCs and the immunogenicity profile, for development of new combined therapeutic strategies. Full article

Mycobacterium tuberculosis (Mtb) vaccines are designed to prevent infection, prevent reactivation of latent infection, and/or provide adjuvant therapy to standard TB treatment for active Mtb. Emerging vaccine technologies include reverse vaccinology, DNA and RNA vaccines, subunit vaccines, and multi-epitope vaccines. Currently, many different types of vaccine candidates are in clinical trials, though, to date, BCG remains the only approved Mtb vaccine. Mtb has a complex genome with numerous antigens, but not all are equally effective in eliciting immunity, so a critical challenge is the selection of antigens and epitopes that are most likely to induce a long-term, broad-spectrum protective immune response. Multi-epitope vaccines (MEVs) represent a new event horizon in vaccine development. Bioinformatic computer modeling is being used to maximize efficacy and minimalize adverse effects. Although no multi-epitope vaccines have proceeded to in vivo clinical trials, three candidate MEVs have made it through in silico tests. Multi-epitope vaccine candidate PP13138R, containing 13 HTL epitopes, 13 CTL epitopes, and 8 B cell epitopes in addition to both TLR2 and TLR4 agonists, aims to elicit a broad immune response that could address both active and latent Mtb infection. Similarly, immunoinformatic data were used to design and validate another MEV candidate based on the biomarker PE_PGRS17 with four B cell, nine HTL, and six CTL linked epitopes, with a griselimycin sequence as the adjuvant. A third novel prophylactic and therapeutic MEV was developed that targets Ag85A, AG85B, ESAT-6, and CFP-10 proteins with 12 CTL, 25 HTL, and 21 LBL epitopes with a CpG adjuvant. Full article

Upper gastrointestinal (GI) malignancies, including esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinomas, remain a major global health concern, with poor overall survival and high recurrence rate despite aggressive treatment. Patients with very early tumors (cT1a) can benefit from endoscopic therapy. However, patients with locally advanced disease require multimodal therapies that may combine surgery, radiation, and systemic therapies. This review provides a comprehensive overview of recent advancements in the treatment of locally advanced upper GI adenocarcinomas. Surgical resection remains the cornerstone of curative treatment, with perioperative chemotherapy emerging as the standard of care. While preoperative chemoradiation has demonstrated some benefits in esophageal and GEJ cancers, recent data suggest a more limited role for radiation going forward. Immunotherapy has shown some promise in both the adjuvant and perioperative settings but has yet to establish definitive survival benefit. The integration of HER2-targeted therapies into treatment regimens for HER2-positive locally advanced gastroesophageal cancers has not yielded significant improvements, underscoring the need for more effective strategies. Ongoing research focuses on better predictive biomarkers, personalized treatment approaches, and potential organ preservation strategies for patients achieving a clinical complete response. Continued advancements in treatment modalities and precision medicine are critical to improving survival for patients with locally advanced upper GI adenocarcinomas. Full article

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

Colorectal cancer (CRC) is the third-most common cancer globally and a leading cause of cancer-related deaths. While the prognostic and predictive roles of RAS mutations in advanced CRC are well-established, their significance in early-stage CRC remains a topic of debate. Studies have been conducted for many years on clinical and pathological parameters that may be associated with RAS mutation, and there are inconsistent results in this regard. Currently, the only biomarker used in early-stage CRC is microsatellite status. KRAS mutations are detected in 40–50% of patients with colorectal cancer. RAS activating mutations cause loss of EGFR regulation by acting on the RAS/RAF/MAPK signaling pathways. In advanced colorectal cancer, these mechanisms cause a decrease in the effectiveness of EGFR inhibitors. However, studies on patients with early-stage colorectal cancer have inconsistent results. This review highlights the prognostic and clinical significance of KRAS mutations in early-stage CRC, particularly in MSS tumors. In the MSS group, KRAS mutations were associated with shorter TTR and OS compared to DWT patients. In contrast, in the MSI-H group, KRAS mutations showed no prognostic effect in TTR and OS. However. KRAS mutations were associated with shorter SAR in both MSI-H and MSS groups of patients. The findings underscore the need for routine molecular profiling, including KRAS and MSI status, to refine risk stratification and guide adjuvant therapy decisions. Further studies are warranted to explore targeted therapeutic approaches for KRAS-mutant CRC in the adjuvant setting. Full article

Background: Approximately 25–30% of non-small-cell lung cancer (NSCLC) patients are diagnosed when the disease is still resectable, although the risk of recurrence is significant. Recently, approaches based on targeted agents or immune checkpoint inhibitors (ICIs) have modified the management of such patients. However, some questions remain unanswered. Objectives: Our aim is to assess the current evidence on approaches involving targeted agents and ICIs in resectable NSCLC, to provide an up-to-date overview of the subject, and to identify areas of current debate, Methods: We analyzed randomized trials on ICIs and targeted therapies in early-stage NSCLC, published or presented at international oncology meetings throughout the last 5 years. Results: Osimertinib and alectinib have shown robust results in the adjuvant setting for molecularly identified patient subgroups, while ICIs have achieved robust data in the neoadjuvant/perioperative setting, with less consistent data on the pure adjuvant approach. Circulating tumor DNA levels may offer a possible biomarker for therapeutic decisions, albeit more prospective data are needed. Conclusions: Targeted agents and ICIs are revolutionizing early-stage NSCLC, similarly to what was observed in advanced disease. Prospective studies designed to compare neoadjuvant, adjuvant, and perioperative approaches and to assess the role of circulating biomarkers are warranted. Full article

Urothelial carcinoma (UC) is the most common histological subtype of bladder tumors; however, bladder cancer represents a heterogeneous group of diseases with at least 40 distinct histological subtypes. Among these, the 2022 World Health Organization classification of urinary tract tumors identifies a range of less common subtypes of invasive UC, formerly known as variants, which are considered high-grade tumors, including squamous cell, small-cell, sarcomatoid urothelial, micropapillary, plasmacytoid, and urachal carcinomas, and adenocarcinoma. Their accurate histological diagnosis is critical for risk stratification and therapeutic decision-making, as most subtype histologies are associated with poorer outcomes than conventional UC. Despite the importance of a precise diagnosis, high-quality evidence on optimal treatments for subtype histologies remains limited owing to their rarity. In particular, neoadjuvant and adjuvant chemotherapy have not been well characterized, and prospective data are scarce. For advanced-stage diseases, clinical trial participation is strongly recommended to address the lack of robust evidence. Advances in molecular pathology and the development of targeted therapies and immunotherapies have reshaped our understanding and classification of bladder cancer subtypes, spurring efforts to identify predictive biomarkers to guide personalized treatment strategies. Nevertheless, the management of rare bladder cancer subgroups remains challenging because they are frequently excluded from clinical trials. For localized disease, curative options such as surgical resection or radiotherapy are available; however, treatment options become more limited in recurrence or metastasis, where systemic therapy is primarily used to control disease progression and palliate symptoms. Herein, we present recent advances in the management of urothelial and non-urothelial bladder cancer subtypes and also explore the current evidence guiding their treatment and emphasize the challenges and perspectives of future therapeutic strategies. Full article

Melanoma is one of the most malignant cancers, and the global incidence of cutaneous melanoma is increasing. While melanomas are highly prone to metastasize if diagnosed late, early detection and treatment significantly reduce the risk of mortality. Identifying patients at higher risk of metastasis, who might benefit from early adjuvant therapies, is particularly important, especially with the advent of new melanoma treatments. Therefore, there is a pressing need to develop additional prognostic biomarkers for melanoma to improve early stratification of patients and accurately identify high-risk subgroups, ultimately enabling more effective personalized treatments. Recent advances in melanoma therapy, including targeted treatments and immunotherapy, have underscored the importance of biomarkers in determining prognosis and predicting treatment response. The clinical application of these markers holds the potential for significant advancements in melanoma management. Various tumor-derived genetic, proteomic, and cellular components are continuously released into the bloodstream of cancer patients. These molecules, including circulating tumor DNA and RNA, proteins, tumor cells, and immune cells, are emerging as practical and precise liquid biomarkers for cancer. In the current era of effective molecular-targeted therapies and immunotherapies, there is an urgent need to integrate these circulating biomarkers into clinical practice to facilitate personalized treatment. This review highlights recent discoveries in circulating melanoma biomarkers, explores the challenges and potentials of emerging technologies for liquid biomarker discovery, and discusses future directions in melanoma biomarker research. Full article

Therapeutic strategies for early-stage non-small cell lung cancer (NSCLC) are advancing, with immune checkpoint inhibitors (ICIs) and targeted therapies making their way into neoadjuvant and adjuvant settings. With recent advances, there was a need for multidisciplinary lung cancer healthcare providers from across Ontario to convene and review recent data from practical and implementation standpoints. The focus was on the following questions: (1) To what extent do patient (e.g., history of smoking) and disease (e.g., histology, tumor burden, nodal involvement) characteristics influence treatment approaches? (2) What are the surgical considerations in early-stage NSCLC? (3) What is the role of radiation therapy in the context of recent evidence? (4) What is the impact of biomarker testing on treatment planning? Ongoing challenges, treatment gaps, outstanding questions, and controversies with the data were assessed through a pre-meeting survey, interactive cases, and polling questions. By reviewing practice patterns across Ontario cancer centers in the context of evolving clinical data, Health Canada indications, and provincial (Cancer Care Ontario [CCO]) funding approvals, physicians treating lung cancer voiced their opinions on how new approaches should be integrated into provincial treatment algorithms. This report summarizes the forum outcomes, including pre-meeting survey and polling question results, as well as agreements on treatment approaches based on specific patient scenarios. Full article

Background: The prognosis of patients diagnosed with locally advanced and metastatic gastric and esophago-gastric junction cancer is critical. The optimal choice of systemic therapy is essential to optimize survival outcomes. Methods: A comprehensive literature review via PubMed and analysis of major oncology congresses (European Society for Medical Oncology and American Society of Clinical Oncology websites) were conducted to ascertain the current status and latest developments in the systemic treatment of patients with localized or advanced gastric and esophago-gastric junction adenocarcinoma. Results: While neoadjuvant and perioperative chemotherapy for localized tumor stages is the preferred approach in the Western Hemisphere, adjuvant chemotherapy remains the preferred course of action in East Asia. The administration of chemotherapy, typically in the form of combinations comprising platinum and fluoropyrimidine compounds in combination with docetaxel, represents a standard of care. Investigations are underway into the potential of immunotherapy and other biologically targeted agents in the perioperative setting. To select the most appropriate therapy for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is essential to determine biomarkers such as HER2 expression, PD-L1 combined positive score (CPS) (combined positive score), Claudin 18.2, and microsatellite instability (MSI). In the present clinical context, the standard first-line therapy is a combination of fluoropyrimidine and a platinum derivative. The selection of chemotherapy in combination with antibodies is contingent upon the specific biomarker under consideration. Conclusions: This article reviews the current state of the art based on recent clinical trial results and provides an outlook on the future of systemic therapy. Full article

Background/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, the BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of the nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusions: Our preliminary study suggests that oncological treatments modify the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression. Full article

The search for dependable molecular biomarkers to enhance routine clinical practice is a compelling challenge across all oncology fields. Urothelial bladder carcinoma, known for its significant heterogeneity, presents difficulties in predicting responses to systemic therapies and outcomes post-radical cystectomy. Recent advancements in molecular cancer biology offer promising avenues to understand the disease’s biology and identify emerging predictive biomarkers. Stratifying patients based on their recurrence risk post-curative treatment or predicting the efficacy of conventional and targeted therapies could catalyze personalized treatment selection and disease surveillance. Despite progress, reliable molecular biomarkers to forecast responses to systemic agents, in neoadjuvant, adjuvant, or palliative treatment settings, are still lacking, underscoring an urgent unmet need. This review aims to delve into the utilization of current and emerging molecular signatures across various stages of urothelial bladder carcinoma to predict responses to systemic therapy. Full article

The intersection of immunology and nanotechnology has provided significant advancements in biomedical research and clinical applications over the years. Immunology aims to understand the immune system’s defense mechanisms against pathogens. Nanotechnology has demonstrated its potential to manipulate immune responses, as nanomaterials’ properties can be modified for the desired application. Research has shown that nanomaterials can be applied in diagnostics, therapy, and vaccine development. In diagnostics, nanomaterials can be used for biosensor development, accurately detecting biomarkers even at very low concentrations. Therapeutically, nanomaterials can act as efficient carriers for delivering drugs, antigens, or genetic material directly to targeted cells or tissues. This targeted delivery improves therapeutic efficacy and reduces the adverse effects on healthy cells and tissues. In vaccine development, nanoparticles can improve vaccine durability and extend immune responses by effectively delivering adjuvants and antigens to immune cells. Despite these advancements, challenges regarding the safety, biocompatibility, and scalability of nanomaterials for clinical applications are still present. This review will cover the fundamental interactions between nanomaterials and the immune system, their potential applications in immunology, and their safety and biocompatibility concerns. Full article