Anaplastic thyroid cancer (ATC) is a rare endocrine cancer and one of the most lethal malignancies with only few treatment options. Most patients present with advanced and unresectable disease, and the median survival is approximately three months. In recent years, systemic treatments have become available for a subgroup of patients with ATC harboring targetable variants, such as BRAF/MEK inhibitors for patients with pathogenetic BRAFV600E variants. However, only a small proportion of patients with ATC are eligible for these treatments, and most treated patients develop resistant and progressive disease. Hence, an urgent need remains for new treatment approaches. Accumulating evidence underlines the roles of systemic inflammation, immunosuppressive and protumoral immune cells tumor infiltration, and elevated numbers of circulating proinflammatory myeloid immune cells in tumor angiogenesis, metastasis, and disease progression of ATC. In this review, we highlight recent advances in understanding the pathogenesis of ATC and summarize latest trends in systemic treatments for patients with ATC. Moreover, based on these developments in understanding the pathophysiology of the disease, we propose how targeting different protumoral processes could lead to future treatment modalities for patients with ATC, with a specific focus on inflammatory processes and the innate immune system.
Oesophagogastric junction adenocarcinoma (OGJ AC) represents an increasingly prevalent malignancy for which treatment recommendations remain challenging, as patients are frequently included within trials addressing gastric or oesophageal cancer. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) published between 2000 and 2025 including patients with OGJ AC to provide a comprehensive assessment of contemporary treatment strategies for this disease across all stages. A total of 100 high-quality RCTs including more than 13,000 patients with OGJ tumours were identified. In localized disease, 36 studies evaluated surgical procedures, adjuvant/neoadjuvant/perioperative treatments and definitive approaches. Surgery is still the cornerstone of curative treatment, increasingly incorporating minimally invasive techniques. Perioperative chemotherapy and chemoimmunotherapy represent standard approaches, while neoadjuvant chemoradiotherapy followed by adjuvant nivolumab represents an alternative strategy. In advanced disease, 64 studies assessed systemic therapies in first/second/third lines or palliative interventions. Platinum-fluoropyrimidine chemotherapy persists as the backbone of first-line treatment, with treatment intensification guided by biomarkers. While the benefit of trastuzumab in HER2-positive tumours appears greater in OGJ than in gastric cancer, the opposite pattern is observed with zolbetuximab in CLDN18.2-positive tumours. Several trials testing anti-PD-1 therapies confirm their activity in OGJ AC, despite the predictive value of PD-L1 appearing uncertain in this anatomical subgroup. In later lines, paclitaxel plus ramucirumab, trastuzumab deruxtecan for HER2-positive disease, and trifluridine-tipiracil remain established options. The available evidence suggests clinically meaningful differences in treatment efficacy according to tumour location, supporting the consideration of OGJ AC as a distinct disease entity. Dedicated OGJ AC trials incorporating standardized anatomical classification are needed to improve outcomes in this aggressive disease.
