Onco

Background: Colorectal cancer (CRC) is a major contributor to cancer-related mortality globally. Despite significant advances in therapeutic strategies, CRC continues to exhibit high recurrence rates. This underscores the urgent need for reliable, non-invasive biomarkers to improve diagnostic precision, early detection, and clinical outcomes. Methods: Gene expression datasets from the GEO database were analyzed to identify differentially expressed genes between CRC and normal tissue samples. Hub genes were identified through an integrative approach combining module membership, gene significance, differential expression, and network centrality. Prognostic significance was assessed via overall survival analysis, and diagnostic utility through ROC curve and AUC. Further integrative analysis included immune cell infiltration, promoter methylation, genetic alterations, and regulatory network construction. Results: An integrated approach identified 989 candidate hub genes. Of these, 128 genes demonstrated significant prognostic potential: 67 were associated with poor overall survival and 61 with favorable outcomes. These genes exhibited patterns of co-expression and positive correlations with immune cell infiltration, particularly B cells, dendritic cells, macrophages, mast cells, and monocytes. Twenty-three hub genes, including MACC1, YEATS4, HMMR, TIGD2, CENPE, GNL3, GMPS, NCAPG, RRM1, DLGAP5, YARS2, CCT8, MET, ZWILCH, KPNA2, KIF15, TRUB1, AURKA, NUDT21, PBK, TOMM20, KIAA1549, and MCM4, showed high diagnostic accuracy in distinguishing CRC from normal tissues. Furthermore, 18 hub genes exhibited statistically significant differential promoter methylation and may serve as promising candidates for epigenetic biomarkers in CRC. Conclusions: Our findings provide a strong foundation for developing more accurate multi-gene prognostic and diagnostic panels and personalized therapies for CRC, with the goal of improving clinical outcomes and reducing the global burden of this disease. Full article

Gallbladder cancer (GBC), an aggressive malignancy of the biliary tract, is characterized by pronounced geographical variation and a poor prognosis, with a five-year survival rate below 20%. Despite its low global incidence, it ranks as the fifth most prevalent gastrointestinal cancer. The aim of this review is to provide a comprehensive understanding of the molecular mechanisms underpinning GBC progression, with a particular focus on the pivotal role of transcription factors (TFs) in its pathogenesis. This review delineates how aberrant regulation of TFs contributes to tumor initiation, progression, and therapeutic resistance, and to discuss the translational potential of targeting these factors for clinical benefit. Tumor suppressor TFs such as p53 and p16 frequently undergo genetic alterations, including mutations, deletions, or epigenetic silencing, leading to impaired cell cycle control, DNA repair, and apoptosis. Conversely, oncogenic TFs including TCF4, MYBL2, NF-kB, AP-1, Snail, c-MYC, SP1, FOXK1, KLF-5, STAT3 and BIRC7 are often upregulated in GBC, promoting unchecked proliferation, epithelial–mesenchymal transition (EMT), metastasis, and therapeutic resistance. This review aims to bridge current molecular insights with emerging therapeutic approaches, with particular emphasis on innovative interventions such as proteolysis-targeting chimeras (PROTACs), RNA-based therapeutics, CRISPR-driven genome editing, and epigenetic modulators, which collectively represent promising strategies for achieving more effective and personalized treatment outcomes in patients with GBC. Full article

The inflammatory milieu surrounding tumors plays a pivotal yet paradoxical role in promoting carcinogenesis. Rather than simply acting as a host defense mechanism, chronic low-grade inflammation actively nurtures tumor development and supports hallmarks such as sustained proliferative signaling, apoptosis resistance, angiogenesis, and metastasis. Obesity, characterized by a chronic inflammatory state, exacerbates this tumor-promoting environment through metabolic imbalances like insulin resistance, hyperglycemia, and dyslipidemia. These conditions stimulate oncogenic signaling pathways and reshape the tumor microenvironment. Obesity-associated cytokines, altered adipokines, and insulin-related growth signals synergistically enhance processes such as epithelial-to-mesenchymal transition (EMT) and matrix remodeling. This review explores the mechanistic interplay between obesity-induced inflammation and insulin resistance in cancer progression, discusses the molecular pathways involved, and highlights emerging therapeutic approaches targeting these intersecting tumor promotion axes. Full article

Background: Ovarian cancer remains a major contributor to cancer-related morbidity and mortality worldwide. Primary cytoreductive surgery is the cornerstone of treatment, and accurate preoperative assessment of tumor resectability is critical to guiding optimal therapeutic strategies in patients with advanced tubo-ovarian cancer. Methods: A narrative review about the role of ultrasound for assessing tumor spread and prediction of tumor resectability was performed. Results: The ISAAC study represents the largest prospective multicenter trial to date comparing the diagnostic performance of ultrasound (US), computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) in predicting non-resectability, using surgical and histopathological findings as the reference standard. Key strengths of the study include the use of standardized imaging and intraoperative reporting protocols across ESGO-accredited high-volume oncologic centers. All three imaging modalities were performed within four weeks prior to surgery by independent, blinded expert operators. US demonstrated diagnostic accuracy comparable to that of CT and WB-DWI/MRI. The study also defined modality-specific thresholds for the Peritoneal Cancer Index (PCI) and Predictive Index Value (PIV), offering quantitative tools to support surgical decision-making. A noteworthy secondary finding was patient preference: in a cohort of 144 participants who underwent all three imaging modalities, nearly half preferred US, while WB-DWI/MRI was the least favored due to discomfort and examination duration. Conclusions: The ISAAC study represents a significant advancement in imaging-based prediction of surgical non-resectability in tubo-ovarian cancer. Its findings suggest that, in expert hands, ultrasound can match or even surpass cross-sectional imaging for preoperative staging, supporting its integration into routine clinical practice, particularly in resource-constrained settings. Full article

Colorectal liver metastases (CRLM) management remains a complex conundrum in the context of potential curable disease. The combination of systemic therapy and surgery, with overall survival outcomes up to 58% at five years, has become the gold standard. Locoregional therapies have gained evidence in complementing surgery or even substituting it in selected cases. Adequate patient selection is paramount, but prognostic models have certain limitations that prevent their full implementation in clinical practice. A plethora of prognostic factors exists, with variable evidence supporting their definitive role. Thus, CRLM management decisions frequently vary depending on multidisciplinary team experience and hospital access to systemic and locoregional treatments. Definition of resectability has evolved in recent years due to technical developments in surgical and non-surgical approaches. Complexity is added when trying to fully understand the integration between local and systemic treatment. Whereas evidence in the context of resectable disease has been attempted in several phase III trials, definitive conclusions regarding the best approach to potentially resectable disease cannot be drawn. In addition, liver transplantation has gained evidence and is proposed in selected patients, raising a challenge regarding its integration and wider implementation. In this review, current standards in the management of CRLM regarding patient selection, resectability, surgical and non-surgical locoregional strategies, as well as the best systemic approach are covered. Full article

Pancreatic cancer is expected to become the second leading cause of death by 2030 in Western countries. There is a need to pinpoint high-risk populations since extensive screening would be economically impractical. Methods: This study, conducted on liquid biopsies of patients affected by pancreatic ductal adenocarcinoma (PDAC), sequenced, by NGS, the main genes involved in pancreatic carcinogenesis. Results: The study was discontinued due to a low recruitment rate. NGS analysis, conducted on included patients, revealed the TP53 variant rs1042522 in 30 out of 35 patients, with a cytosine (C) replaced by a guanine (G), hence inserting an Arginine in the final protein instead of a Proline. The presence of the rs1042522 variant confers an odds ratio of 6.11 for PaC and an OR of 20 for homozygosity G/G when comparing our cohort of PaC patients to a healthy population from the 1000GenomeProject. Conclusion: These findings could identify a very-high-risk population deserving of being screened for PDAC, even though a wider validation of rs1042522 as a risk factor is needed. Impact: These preliminary data may open the way for identification of a population more prone to developing pancreatic cancer. Full article

Background: Despite advances in gene-targeted and immunotherapies, many aggressive cancers—including glioblastoma and triple-negative breast cancer—remain refractory to treatment. Mounting evidence implicates metabolic reprogramming, especially dysregulation of glucose and glutamine metabolism, as a core hallmark of tumor progression. Natural compounds with metabolic-modulatory effects have emerged as promising adjuncts in oncology. Research Question and Objectives: This review investigates the following question: How can metabolic-targeted therapies—particularly those modulating the Warburg effect and glutamine metabolism—improve cancer treatment outcomes, and what role do natural compounds play in this strategy? The objectives were to (1) evaluate the therapeutic potential of metabolic interventions targeting glucose and glutamine metabolism, (2) assess natural compounds with metabolic regulatory activity, (3) examine integration of metabolic-targeted therapies with conventional treatments, and (4) identify metabolic vulnerabilities in resistant malignancies. Methods: A qualitative systematic review (QualSR) was conducted following PRISMA guidelines. A total of 87 peer-reviewed studies published between 2000 and 2024 were included. Inclusion criteria required clearly defined mechanistic or clinical endpoints and, for clinical trials, sample sizes ≥ 30. Data extraction focused on tumor response, survival, metabolic modulation, and safety profiles. Results: Curcumin significantly reduced serum TNF-α and IL-6 (both p = 0.001) and improved antioxidant capacity (p = 0.001). EGCG downregulated ERα (p = 0.002) and upregulated tumor suppressors p53 and p21 (p = 0.001, p = 0.02). High-dose intravenous vitamin C combined with chemoradiotherapy yielded a 44.4% pathologic complete response rate in rectal cancer. Berberine suppressed Akt/mTOR signaling and glutamine transporter SLC1A5 across tumor types (q < 10⁻¹⁰). However, poor bioavailability (e.g., EGCG t½ = 3.4 ± 0.3 h) and systemic toxicity limit their standalone clinical application. Conclusions: Metabolic-targeted therapies—particularly natural compounds acting on glucose and glutamine pathways—offer a viable adjunct to standard cancer therapies. Clinical translation will require biomarker-driven patient stratification, improved delivery systems, and combination trials to optimize the therapeutic impact in treatment-resistant cancers. Full article

The development of molecular profiling approaches for AML patients such as whole genome sequencing, whole exome sequencing and transcriptomic sequencing have greatly contributed to better understanding of leukemia development, progression and treatment responsiveness/resistance. These studies have generated a new knowledge about driver events operating in AML that can be translated into clinics, thus favoring the mutations; using this approach, more than 50% of older AML patients display molecular alterations, such as IDH1, IDH2, FLT3 (FLT3-TKD and FLT3-ITD), NPM1 and KMT2A rearrangements that can be targeted by specific drugs. Preclinical and clinical studies have supported the use of drugs targeting these molecular alterations as first-line therapy in association with induction chemotherapy in chemotherapy-fit patients or with a hypomethylating agent in association with a Bcl-2 inhibitor (Venetoclax) in chemotherapy-unfit patients. These studies have shown promising results that need to be confirmed through randomized clinical studies specifically involving the enrollment of older AML patients. Full article

Cancer is a public health concern due to the incidence, prevalence, morbidity, and mortality associated with it. While chemotherapy, radiotherapy, surgery, and immunotherapy are common treatments, there is still ongoing research to find targeted and innovative therapies that are more efficacious. The effect of probiotics on cancer progression and treatment has been actively investigated using different in vitro and in vivo models. Similarly, the role of prebiotics alone or in combination with probiotics, referred to as synbiotics, has also been evaluated in the context of cancers. Recently, the therapeutical potential of postbiotics is also being determined. Many studies have demonstrated that these agents can have onco-suppressive effects and can also prevent cancer in some instances. In this review, we summarize the different studies that have utilized these therapeutics in the prevention and treatment of a variety of cancers. We also discuss the different molecular mechanisms that enable these agents to be effective against cancers. Finally, we address safety and the need for more robust clinical trials that will aid in designing strategies involving these biotics in the prevention and treatment of cancer. Full article

Background: Osteosarcoma (OS) is a fast-growing malignant bone tumor that occurs most often in children and teenagers. Development of pulmonary metastasis is the primary cause of treatment failure and mortality. Our previous studies demonstrated that cytoplasmic p27 interacts with PAK1, enhancing PAK1 phosphorylation and promoting OS pulmonary metastasis. However, the cellular functions of p27 and PAK1 are primarily regulated by phosphorylation, and the roles of specific phosphorylation residues in modulating OS metastatic potential remain unclear. Methods: To study tumor invasiveness and lung metastasis, we employed a CRISPR-based knock-in method to introduce specific mutations—p27-T157A, p27-T157D, PAK1-T423E, and PAK1-K299R—into the 143B OS cell line, followed by in vitro invasion and orthotopic xenograft mouse experiments. These residues were selected for their therapeutic potential, as T157 regulates p27 nuclear–cytoplasmic shuttling, while T423 and K299 modulate PAK1 kinase activity. Results: No significant differences in pulmonary metastasis were observed across p27 mutants compared to parental controls. However, the p27-T157D mutant exhibited increased cytoplasmic mislocalization, elevated PAK1-S144 phosphorylation, and enhanced in vitro invasiveness compared to the p27-T157A mutant and parental 143B cells. The PAK1-K299R mutant, designed to be kinase-dead, showed negligible S144 phosphorylation, consistent with loss of kinase activity. Unexpectedly, this mutant displayed increased T423 phosphorylation and in vitro invasiveness, and significantly enhanced pulmonary metastasis in vivo compared to the PAK1-T423E mutant and parental controls. Conclusions: These findings highlight the complexity of targeting specific p27 and PAK1 phosphorylation sites as an anti-metastatic strategy for OS. While p27-T157 phosphorylation influences cytoplasmic localization and invasiveness, it does not significantly alter metastatic outcomes. Conversely, PAK1-T423 phosphorylation is critical in driving OS metastatic potential, and the kinase-dead K299R mutant’s unexpected pro-metastatic effect suggests that kinase-independent mechanisms or compensatory pathways may contribute to metastasis. Our findings suggest the necessity for a more comprehensive understanding of the phosphorylation dynamics of p27 and PAK1 in metastatic OS. They also indicate that conventional kinase inhibition may be insufficient and underscore the potential benefits of alternative or combinatorial therapeutic strategies, such as targeting kinase-independent functions or other upstream kinases involved in these regulatory pathways. Full article

Adenoma-like adenocarcinoma (ALAC) of the colon is a recently recognized histological subtype of colorectal adenocarcinoma, characterized by a villous architecture, low-grade cytologic atypia, and deceptive bland morphology despite its invasive potential, which can mimic non-invasive adenomas, leading to underdiagnosis in limited biopsy samples. Herein, we report the case of an 81-year-old male presenting with right-upper-quadrant pain that was found to have a hepatic abscess and a 4 cm villous lesion in the ascending colon. Histopathological examination of the right hemicolectomy specimen revealed a villous adenocarcinoma with invasion of the muscularis propria, consistent with adenoma-like adenocarcinoma. Isolated loss of PMS2 indicated a mismatch repair deficiency. However, adjuvant therapy was not indicated. The patient remained recurrence-free for three years, until he died from unrelated causes in the context of progressive frailty and comorbidities, with no evidence of cancer progression. This case highlights the diagnostic challenges posed by ALAC and underscores the importance of recognizing its distinct morphological features. Awareness of this entity is essential to avoid misclassification and ensure adequate treatment, especially given its typically favorable prognosis with low metastatic potential. Full article

Prostate cancer exhibits highly variable behavior, from slow-growing localized tumors to aggressive metastatic disease, yet early prognostic indicators remain limited. In this study, we examined B7-H3 (CD276) expression, a molecule linked to immune suppression and cancer progression in diagnostic biopsy specimens from 248 patients with localized or metastatic prostate cancer. We found that elevated B7-H3 levels were significantly more common in metastatic cases and independently associated with reduced overall and disease-specific survival. Moreover, high B7-H3 expression correlated with increased PSA values and higher Gleason grades. These findings endorse B7-H3 as a robust prognostic marker and potential therapeutic target in advanced prostate cancer management. Full article

Prompt and accurate identification of liver metastases from neuroendocrine tumors, arising from the gastrointestinal system and from the pancreas, through the means of both anatomical and functional diagnostic imaging techniques is mandatory. A patient’s prognosis and treatment planning are dependent on these diagnostic procedures. The aim of this narrative review is to depict the common appearance of liver metastases, as well as to depict atypical imaging patterns. Moreover, this review will cover the differential diagnosis between liver metastases from neuroendocrine tumors and other primary and secondary malignant liver lesions, as well as benign liver lesions. Full article

Background: Many patients harbor minimal residual disease (MRD)—small clusters of residual tumor cells that survive therapy and evade conventional detection but drive recurrence. Although advances in molecular and computational methods have improved circulating tumor DNA (ctDNA)-based MRD detection, these approaches face challenges: ctDNA shedding fluctuates widely across tumor types, disease stages, and histological features. Additionally, low levels of driver mutations originating from healthy tissues can create background noise, complicating the accurate identification of bona fide tumor-specific signals. These limitations underscore the need for refined technologies to further enhance MRD detection beyond DNA sequences in solid malignancies. Methods: Profiling circulating cell-free mRNA (cfmRNA), which is hyperactive in tumor and non-tumor microenvironments, could address these limitations to inform postoperative surveillance and treatment strategies. This study reported the development of OncoMRD BREAST, a customized, gene signature-informed cfmRNA assay for residual disease monitoring in breast cancer. OncoMRD BREAST introduces several advanced technologies that distinguish it from the existing ctDNA-MRD tests. It builds on the patient-derived gene signature for capturing tumor activities while introducing significant upgrades to its liquid biopsy transcriptomic profiling, digital scoring systems, and tracking capabilities. Results: The OncoMRD BREAST test processes inputs from multiple cutting-edge biomarkers—tumor and non-tumor microenvironment—to provide enhanced awareness of tumor activities in real time. By fusing data from these diverse intra- and inter-cellular networks, OncoMRD BREAST significantly improves the sensitivity and reliability of MRD detection and prognosis analysis, even under challenging and complex conditions. In a proof-of-concept real-world pilot trial, OncoMRD BREAST’s rapid quantification of potential tumor activity helped reduce the risk of incorrect treatment strategies, while advanced predictive analytics contributed to the overall benefits and improved outcomes of patients. Conclusions: By tailoring the assay to individual tumor profiles, we aimed to enhance early identification of residual disease and optimize therapeutic decision-making. OncoMRD BREAST is the world’s first and only gene signature-powered test for monitoring residual disease in solid tumors. Full article

Background: Clinical imaging is an important part of health care providing physicians with great assistance in patients treatment. In fact, segmentation and grading of tumors can help doctors assess the severity of the cancer at an early stage and increase the chances of cure. Despite that Deep Learning for cancer diagnosis has achieved clinically acceptable accuracy, there still remains challenging tasks, especially in the context of insufficient labeled data and the subsequent need for expensive computational ressources. Objective: This paper presents a lightweight classification and segmentation deep learning model to assist in the identification of cancerous tumors with high accuracy despite the scarcity of medical data. Methods: We propose a multi-task architecture for classification and segmentation of cancerous tumors in the Brain, Skin, Prostate and lungs. The model is based on the UNet architecture with different pre-trained deep learning models (VGG 16 and MobileNetv2) as a backbone. The multi-task model is validated on relatively small datasets (slightly exceed 1200 images) that are diverse in terms of modalities (IRM, X-Ray, Dermoscopic and Digital Histopathology), number of classes, shapes, and sizes of cancer pathologies using the accuracy and dice coefficient as statistical metrics. Results: Experiments show that the multi-task approach improve the learning efficiency and the prediction accuracy for the segmentation and classification tasks, compared to training the individual models separately. The multi-task architecture reached a classification accuracy of 86%, 90%, 88%, and 87% respectively for Skin Lesion, Brain Tumor, Prostate Cancer and Pneumothorax. For the segmentation tasks we were able to achieve high precisions respectively 95%, 98% for the Skin Lesion and Brain Tumor segmentation and a 99% precise segmentation for both Prostate cancer and Pneumothorax. Proving that the multi-task solution is more efficient than single-task networks. Full article

Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF⁺ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles bud from cancer cell surfaces and carry procoagulant factors (phosphatidylserine and TF) on their surface. We review how TF⁺ MPs are generated by tumor cells and amplify the extrinsic coagulation cascade, potentially triggering DIC in patients with advanced gynecologic cancers. Clinical studies have linked el evated TF⁺ MP levels and activity to venous thromboembolism (VTE) in cancer, and small case series suggest dramatically high MP–TF activity in cancer-related DIC. We summarize evidence that TF⁺ MPs from ovarian tumors carry exceptionally high TF procoagulant activity (median ~80 pg/mL), and nearly all patients with cancer-associated VTE or DIC have MP–TF levels above normal. This review discusses diagnostic implications (e.g., measuring MP–TF activity as a biomarker) and treatment strategies (through the reduction in tumors, anticoagulation, and experimental TF inhibitors) in this setting. We also identify gaps in knowledge (standardized MP assays, prospective studies) and propose future directions (targeting MP formation or TF signaling). Two summary tables highlight recent studies of TF⁺ MPs in gynecologic cancer and their clinical outcomes. Illustrative figures depict the TF⁺ MP-triggered coagulation cascade and a conceptual framework for clinical management. Understanding TF⁺ MPs in gynecological cancer could improve the prediction and management of DIC and related thromboses. Full article

Conventional wisdom holds that nuclear oncogenes and tumor suppressors initiate malignant transformation. However, mounting research suggests that mitochondrial dysfunction—rooted in the unique evolutionary history and genetic autonomy of mitochondria—may serve as a more fundamental driver of oncogenesis. This paper proposes a “mitochondria-first” hypothesis of cancer, emphasizing the pivotal role of mitochondrial DNA (mtDNA) mutations, metabolic reprogramming, and immune evasion. By examining the evolutionary conflict between host and mitochondria, evaluating high mtDNA mutation rates, and highlighting the disruptive potential of mitochondrial transfer to immune cells, we outline robust mechanisms through which mitochondria could ignite cancer development. We also discuss emerging diagnostic and therapeutic approaches that target mitochondrial integrity, offering a potential paradigm shift in oncology. Full article