Onco, Volume 5, Issue 4 (December 2025) – 6 articles

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