In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection.

Pancreatic cancer is one of the most aggressive malignancies with limited treatment options thus resulting in high morbidity and mortality. Among all cancers, with a five-year survival rates of only 2–9%, pancreatic cancer holds the worst prognostic outcome for patients. To improve the overall survival, an earlier diagnosis and stratification of cancer patients for personalized treatment options are urgent needs. A minority of pancreatic cancers belong to the spectrum of Lynch syndrome-associated cancers and are characterized by microsatellite instability (MSI). MSI is a consequence of defective mismatch repair protein functions and it has been well characterized in other gastrointestinal tumors such as colorectal and gastric cancer. In the latter, high levels of MSI are linked to a better prognosis and to an increased benefit to immune-based therapies. Therefore, the same therapies could offer an opportunity of treatment for pancreatic cancer patients with MSI. In this review, we summarize the current knowledge about immune-based therapies and MSI in pancreatic cancer.

Gastric cancer (GC) is still one of the most aggressive cancers with a few targetable alterations and a dismal prognosis. A liquid biopsy allows for identifying and analyzing the DNA released from tumor cells into the bloodstream. Compared to tissue-based biopsy, liquid biopsy is less invasive, requires fewer samples, and can be repeated over time in order to longitudinally monitor tumor burden and molecular changes. Circulating tumor DNA (ctDNA) has been recognized to have a prognostic role in all the disease stages of GC. The aim of this article is to review the current and future applications of ctDNA in gastric adenocarcinoma, in particular, with respect to early diagnosis, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision choice and therapeutic monitoring. Although liquid biopsies have shown potentiality, pre-analytical and analytical steps must be standardized and validated to ensure the reproducibility and standardization of the procedures and data analysis methods. Further research is needed to allow the use of liquid biopsy in everyday clinical practice.

Diarrhoea is one of the main side effects that cancer patients face. The literature showsthat the incidence of chemotherapy (CT)-induced diarrhoea (grade 3–4) in treated patients is in the range of 10–20%, particularly after 5-fluorouracil (5-FU) bolus or some combination therapies of irinotecan and fluoropyrimidines. The aim of the present study was to evaluate the clinical effectiveness of Lactobacillus kefiri LKF01 (Kefibios^®) in the prevention or treatment of CT-related diarrhoea in the cancer population. We conducted a prospective observational study. Patients enrolled were adults treated for at least four months with 5-FU-based CT. Kefibios^® was administered to patients every day. The primary outcome was the evaluation of the incidence of grade 3–4 CT-induced diarrhoea. We included 76 patients in the final analysis. A 6.6% incidence of high-grade diarrhoea was found in the evaluated population (4.7% of patients treated with 5-FU-based therapy and 8.5% of patients treated with capecitabine-based CT). The overall incidence of high-grade diarrhoea observed was higher in the 1st and 2nd cycles (3.9%), with a subsequent sharp reduction from the 3rd cycle (1.3%) and negativisation from the 5th cycle. Lactobacillus kefiri LKF01 (Kefibios^®) is safe and effective in preventing severe diarrhoea in cancer patients receiving 5-FU or capecitabine-based treatment.

Metastatic gastric cancer (GC) still represents a critical clinical challenge, with limited treatment options and a poor prognosis. Most patients are diagnosed at advanced stages, limiting the chances of surgery and cure. The identification of molecular targets and the possibility of combining immune checkpoint inhibitors with chemotherapy have recently reshaped the therapeutic landscape of metastatic gastric cancer. The new classification of gastric cancer, mainly based on immunologic and molecular criteria such as programmed cell death 1 (PD-1), microsatellite instability (MSI), and human epidermal growth factor receptor 2 (HER2), has made it possible to identify and differentiate patients who may benefit from immunotherapy, targeted therapy, or chemotherapy alone. All relevant and available molecular and immunological targets in clinical practice for the systemic treatment of this disease are presented. Particular attention is given to possible future approaches, including circulating tumor DNA (ctDNA) for therapeutic monitoring, new targeting agents against molecular pathways such as fibroblast growth factor receptor (FGFR) and MET, chimeric antigen receptor (CAR)-T cells, and cancer vaccines. This review aims to provide a comprehensive understanding of current targets in advanced gastric cancer and to offer valuable insights into future directions of research and clinical practice in this challenging disease.

Circulating tumour DNAs and non-coding RNAs present in body fluids have been under investigation as tools for cancer diagnosis, disease monitoring, and prognosis for many years. These so-called liquid biopsies offer the opportunity to obtain information about the molecular make-up of a cancer in a minimal invasive way and offer the possibility to implement theranostics for precision oncology. Furthermore, liquid biopsies could overcome the limitations of tissue biopsies in capturing the complexity of tumour heterogeneity within the primary cancer and among different metastatic sites. Liquid biopsies may also be implemented to detect early tumour formation or to monitor cancer relapse of response to therapy with greater sensitivity compared with the currently available protein-based blood biomarkers. Most colorectal cancers are often diagnosed at late stages and have a high mortality rate. Hence, biomolecules as nucleic acids present in liquid biopsies might have prognostic potential and could serve as predictive biomarkers for chemotherapeutic regimens. This review will focus on the role of circulating tumour DNAs and non-coding RNAs as diagnostic, prognostic, and predictive biomarkers in the context of colorectal cancer.