Annexin A2 (ANXA2) is a protein that is involved in many physiological and pathological cellular processes. There is compelling evidence that its dysregulated expression, be it up- or downregulation, contributes to the oncogenesis of various neoplasms, including those of the digestive system. The present review summarizes the current knowledge on the role of ANXA2 in the main tumors of the digestive system. The clinical significance of ANXA2 is primordial, due to its potential use as a diagnostic and prognostic biomarker, and as a part of therapeutic protocols. Certain preclinical studies have shown that inhibiting ANXA2 or disrupting its interactions with key molecules can suppress tumor growth, invasion, and metastasis, as well as increase the cancer cells’ sensitivity to treatment in various cancers. Further research is needed to fully elucidate the complex role of ANXA2 in the carcinogenesis of tumors of the digestive system, and to translate these findings into clinical applications for improved diagnosis, prognosis, and treatment.

Cholangiocarcinoma consists of a heterogeneous group of malignancies with generally poor prognoses. Immunotherapy has emerged in the treatment landscape of many tumors, offering survival benefits, ... Plain language summary Cholangiocarcinomas are a group of rare tumors. Survival time is limited, due to late diagnosis and advanced symptoms. The small number of patients makes it difficult to carr...

Defining predictive biomarkers for targeted therapies and optimizing anti-tumor immune response is a main challenge in ongoing investigations. Progastrin has been studied as a potential biomarker for detecting and diagnosing various malignancies, and its secretion has been associated with cell proliferation in the gastrointestinal tract that may promote tumorigenesis. Progastrin is a precursor molecule of gastrin, synthesized as pre-progastrin, converted to progastrin after cleavage, and transformed into amidated gastrin via biosynthetic intermediates. In cancer, progastrin does not maturate in gastrin and becomes a circulating and detectable protein (hPG80). The development of cancer is thought to be dependent on the progressive dysregulation of normal signaling pathways involved in cell proliferation, thus conferring a growth advantage to the cells. Understanding the interaction between progastrin and the immune system is essential for developing future cancer strategies. To that end, the present review will approach the interlink between gastrointestinal cancers and progastrin by exploring the underlying molecular steps involved in the initiation, evolution, and progression of gastrointestinal cancers. Finally, this review will focus on the clinical applications of progastrin and investigate its possible use as a diagnostic and prognostic tumor circulating biomarker for disease progression and treatment effectiveness, as well as its potential role as an innovative cancer target.

Background and Objectives: Relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL) remain associated with poor outcomes despite advances in chemoimmunotherapy and chimeric antigen receptor (CAR) T-cell therapy. Many patients are ineligible for or relapse after cellular therapies, highlighting the need for effective off-the-shelf immunotherapeutic approaches. CD20 × CD3 bispecific antibodies (BsAbs) redirect endogenous T cells against malignant B cells and have emerged as a promising therapeutic class in B-NHL. To summarize current clinical evidence regarding mosunetuzumab, glofitamab, epcoritamab, and odronextamab in B-NHL, focusing on efficacy, safety, and emerging therapeutic applications. Materials and Methods: A structured review of published phase I–III clinical trials evaluating the four currently approved CD20 × CD3 BsAbs in B-NHL was conducted. Efficacy outcomes, durability of response, and safety data were assessed across indolent and aggressive lymphoma subtypes. Results: CD20 × CD3 BsAbs demonstrated substantial and durable clinical activity in heavily pretreated B-NHL, including patients with prior CAR T-cell exposure. Mosunetuzumab showed high response rates and durable remissions in follicular lymphoma (FL), while glofitamab demonstrated significant efficacy in aggressive lymphomas, particularly diffuse large B-cell lymphoma (DLBCL). Epcoritamab exhibited consistent activity across lymphoma subtypes with favorable tolerability supported by subcutaneous administration and step-up dosing. Odronextamab also demonstrated clinically meaningful responses in both FL and DLBCL, including high-risk populations. Across studies, cytokine release syndrome (CRS) was the most common adverse event, predominantly low grade and manageable with established mitigation strategies. Immune effector cell-associated neurotoxicity syndrome (ICANS) was uncommon. Infections and hematologic toxicities, particularly neutropenia, represented clinically relevant adverse events across all treatment programs, highlighting the need for special supportive care. Conclusions: CD20 × CD3 BsAbs represent a major therapeutic advancement in R/R B-NHL, combining high clinical activity, manageable toxicity, and off-the-shelf availability. Their expanding integration into earlier treatment settings and combination strategies is expected to further reshape the therapeutic landscape of B-NHL.

Esophageal cancer (EC) is a highly aggressive gastrointestinal malignancy, with a notable increase in incidence over recent decades, representing a significant global health burden. The main histological subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with the former being closely associated with gastroesophageal reflux disease, Barrett’s esophagus, and obesity, and its incidence continues to increase in Western populations. The rising incidence of EC, combined with poor survival rates, underscores the need for new therapeutic approaches. A deeper understanding of the molecular basis of this prevalent malignancy may open new avenues for optimal therapeutic strategies, with immunotherapy now central in several clinical trials. Understanding the interplay between the tumor microenvironment (TME) and disease progression is pivotal for managing this malignancy, which remains highly challenging. This review highlights the role of the TME in EAC progression and drug resistance, and recent therapeutic advances.

Glioblastoma multiforme is a malignant central nervous system (CNS) disease with dismal prognosis. Current treatment modalities only offer modest activity and usually of short duration, so there is an urgent need for the conduct of clinical trials exploring new treatment options and modalities. The vincristine-irinotecan-temozolomide and bevacizumab (VITb) regimen is an option of special interest, as it has produced encouraging results in young patients with various relapsed/refractory childhood and adolescence solid tumors, with an acceptable toxicity profile. With the current report, we present the case of a young male patient who was treated for GBM in second relapse at out institution, after previous surgical attempts and two radiotherapy sessions in conjunction with temozolomide and experienced a major and long-lasting response, weaned off steroids, to the VITb regimen followed by bevacizumab maintenance. The above case is discussed in the context of the existing literature regarding available evidence of synergy between the drugs used and the activity of certain components of the combination (i.e. combination of temozolomide-irinotecan ± vincristine, or bevacizumab-irinotecan in GBM) or the complete VITb regimen in other pediatric/adolescence solid tumors and the few cases reported with GBM.