Precis. Oncol., Volume 1, Issue 2 (June 2026) – 3 articles

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, with rising incidence and a 5-year survival rate of 13%. Late presentation, early metastasis, and intrinsic resistance constrain the efficacy of cytotoxic chemotherapy, which remains the backbone of PDAC treatment, with only modest survival gains and resistance nearly universal. Although KRAS mutations dominate tumour biology (~90% of cases), PDAC is a heterogeneous disease with distinct molecular subtypes that confer differential therapeutic vulnerabilities. Advances in comprehensive molecular profiling have catalysed a paradigm shift toward precision oncology in PDAC. In KRAS-mutant PDAC, mutation-specific inhibitors have established proof-of-concept, particularly in KRAS G12C disease, while next-generation approaches including KRAS G12D inhibitors, RAS-“ON” inhibitors, proteolysis-targeting chimeras (PROTACs), and KRAS-targeted vaccine strategies are expanding the therapeutic landscape. Combination strategies targeting upstream and downstream effectors of the RAS–MAPK pathway are also being explored to enhance the depth and durability of response. In parallel, KRAS-wild-type PDAC has emerged as a molecularly distinct subgroup enriched for rare but actionable alternative oncogenic fusion drivers including NRG1, NTRK, RET, ALK, and FGFR. Additional molecularly directed strategies targeting HER2 alterations, BRAF mutations, EGFR-dependent signalling, and tumour-selectively exposed surface antigens such as CLDN18.2 are under investigation across PDAC irrespective of KRAS mutation status. Synthetic lethal approaches, including targeting the PRMT5/CDKN2A/MTAP axis, represent a further emerging therapeutic strategy. Germline homologous recombination repair defects, particularly involving BRCA1/2 and PALB2, further define clinically important subsets with sensitivity to platinum chemotherapy and PARP inhibition. This review summarises current and emerging targeted and molecularly directed therapeutic strategies in PDAC, emphasising the importance of molecular stratification and recent advances shaping precision oncology in this historically treatment-refractory disease. Full article

Background/Objectives: Prostate cancer (PCa) incidence is rising, with radical prostatectomy (RP) as the main curative surgery for localised cases, which includes removing seminal vesicles (SV). SV invasion (SVI) predicts poor oncological outcomes, making accurate preoperative staging to identify SVI crucial for surgical planning. This ensures oncological safety by enabling wide excision when needed, while preserving tissue to maintain function. This review synthesises current evidence on pre-biopsy MRI findings and/or clinicopathological parameters to diagnose SVI in PCa. Methods: A literature search (2005–2025) using OVID for studies assessing pre-biopsy MRI findings, with a priori eligibility for clinicopathological or combined MRI–clinicopathological models (index tests), for detecting SVI (outcome) compared to RP histopathology (standard reference) in patients with primary localised PCa (patients). This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was evaluated with QUADAS-2, and pooled diagnostic accuracy metrics and study heterogeneity were analysed. Results: Five studies qualified, while three used binary mpMRI classification and were quantitatively analysed. No eligible studies assessed clinicopathological predictors or combined MRI–clinicopathological models; all included studies evaluated pre-biopsy MRI findings only, and none included high-dimensional radiomics. The pooled sensitivity was 0.66 (95% CI: 0.52–0.78), specificity 0.94 (0.89–0.97), positive predictive value (PPV) 0.76 (0.60–0.87), negative predictive value (NPV) 0.92 (0.85–0.94), and diagnostic odds ratio 30.13 (12.36–73.47), with moderate heterogeneity. All included studies were retrospective cohorts with considerable risk of bias. Conclusions: In the small number of heterogeneous, single-centre retrospective studies available, pre-biopsy MRI findings show high specificity and NPV for preoperative detection of SVI but only moderate sensitivity, which limits its reliability as a standalone tool. The pooled diagnostic accuracy estimates should be interpreted as exploratory. These findings should therefore be interpreted cautiously. Future studies must integrate MRI with clinicopathological data, addressing this key evidence gap before firm conclusions can be drawn or clinical practice changed. Full article

Background/Objectives: The anti-CLDN18.2 antibody zolbetuximab has emerged as a novel therapeutic option for advanced gastric adenocarcinoma. However, robust predictive biomarkers for its efficacy remain an unmet need. Methods: Utilizing the Japanese Center for Cancer Genomics and Advanced Therapeutics database, we retrospectively analyzed the clinical and genomic profiles of 49 patients with gastric adenocarcinoma who received zolbetuximab-containing regimens. In line with Japanese health insurance regulations, these patients were deemed to have CLDN18.2-positive tumors. We explored the association between the objective response rate (ORR) and concurrent genomic alterations, focusing on tumor mutational burden (TMB) and major mutations (TP53, ARID1A, CDH1). Results: The ORR to zolbetuximab-based therapy in this cohort was 22.2%. Statistical analysis revealed a trend toward higher clinical response in patients with lower TMB (median 1.82 in responders vs. 4.0 in non-responders; p = 0.050). Furthermore, patients without a CDH1 single-nucleotide variant also showed a suggestive trend toward better response (p = 0.086). No significant associations were found with TP53 or ARID1A alterations (p = 0.787 and p = 0.239, respectively). Conclusions: Our findings suggest that low TMB and the absence of CDH1 variants may serve as potential predictive biomarkers for response to zolbetuximab in CLDN18.2-positive gastric cancer. Prospective validation is warranted to maximize patient selection for this targeted therapy. Full article