Gastrointestinal stromal tumors (GISTs) are the most common types of malignant mesenchymal tumors in the gastrointestinal tract, with an estimated incidence of 1.5/100.000 per year and 1–2% of gastrointestinal neoplasms. About 75–80% of patients have mutations in the KIT gene in exons 9, 11, 13, 14, 17, and 5–10% of patients have mutations in the platelet-derived growth factor receptor a (PDGFRA) gene in exons 12, 14, 18. Moreover, 10–15% of patients have no mutations and are classified as wild type GIST. The treatment for metastatic or unresectable GISTs includes imatinib, sunitinib, and regorafenib. So far, GIST therapies have raised great expectations and offered patients a better quality of life, but increased pharmacological resistance to tyrosine kinase inhibitors is often observed. New treatment options have emerged, with ripretinib, avapritinib, and cabozantinib getting approvals for these tumors. Nowadays, immune checkpoint inhibitors form a new landscape in cancer therapeutics and have already shown remarkable responses in various tumors. Studies in melanoma, non-small-cell lung cancer, and renal cell carcinoma are very encouraging as these inhibitors have increased survival rates. The purpose of this review is to present alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors).

: Colorectal cancer (CRC) comprises a heterogeneous group of gastrointestinal tract tumors. It is a multifactorial disease, and a plethora of distinct factors are involved in its pathogenesis and pathophysiology. The development of CRC is not limited to genetic changes, but epigenetic and environmental factors are also involved. Among the epigenetic factors, histone deacetylases (HDACs), a group of epigenetic enzymes that regulate gene expression, have been reported to be over-expressed in CRC. HDACs and their inhibitors seem to play an important role in the molecular pathophysiology of CRC. The aim of this review was to define the role of HDAC inhibitors as potential anticancer agents against CRC.

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis, and strategies for clinical management. However, many gastric tumors appear to be resistant to current chemotherapeutic agents. Moreover, a significant number of gastric cancer patients, with a lack of optimal treatment strategies, have reduced survival. In recent years, multiple research data have highlighted the importance of autophagy, an essential catabolic process of cytoplasmic component digestion, in cancer. The role of autophagy as a tumor suppressor or tumor promoter mechanism remains controversial. The multistep nature of the autophagy process offers a wide array of targetable points for designing novel chemotherapeutic strategies. The purpose of this review is to summarize the current knowledge regarding the interplay between gastric cancer development and the autophagy process and decipher the role of autophagy in this kind of cancer. A plethora of different agents that direct or indirect target autophagy may be a novel therapeutic approach for gastric cancer patients.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In damaged liver, TLR4 expression is upregulated, leading to hepatic inflammation and injury. We tried to investigate the role of the two most common single-nucleotide polymorphisms (SNPs) of TLR4 in HCC-genesis. Aged > 18 years old, cirrhotic patients were included in this study. Exclusion criteria were non-HCC tumors and HIV co-infection. TLR4 SNPs association with HCC occurrence was the primary endpoint, and associations with all-cause and liver-related mortality, as well as time durations between diagnosis of cirrhosis and HCC development or death and diagnosis of HCC and death were secondary endpoints. A total of 52 out of 260 included patients had or developed HCC. TLR4 SNPs showed no correlation with primary or secondary endpoints, except for the shorter duration between HCC development and death in patients with TLR4 mutations. Overall, TLR4 SNPs showed no correlation with carcinogenesis or deaths in patients with liver cirrhosis; patients with TLR4 SNPs that developed HCC had lower survival rates, a finding that should be further evaluated.

Pancreatic cancer (PaC) induces a prothrombotic and hypercoagulable state. The aim of this study was to investigate the effect of tinzaparin in combination with chemotherapy. The PaCT (pancreatic cancer and tinzaparin) study was a retrospective observational study that collected data regarding progression free survival (PFS) in advanced or metastatic PaC patients who received thromboprophylaxis with tinzaparin during chemotherapy with nab-paclitaxel (N) and gemcitabine (G). The primary end point was to compare, from already published data, the PFS of patients receiving thromboprophylaxis with tinzaparin with the PFS of patients receiving chemotherapy with N–G but no thromboprophylaxis. Secondary end points were efficacy and safety of anticoagulation. In total, 110 PaC patients, 93% with advanced or metastatic disease, treated with N–G and tinzaparin (10,291 ± 1176 Anti-Xa IU, OD, median duration 8.7, IQR: 5.6–11.9 months) were enrolled. Of these, 52% were males and; the median age was 68 (40–86 years). The tumor was located to in the pancreatic head at in 45% of the patients. The median PFS was 7.9 months (IQR: 5.0–11.8 months). Out of 14 similar studies (involving 2994 patients) identified via systematic search, it was determined that the weighted PFS of patients receiving N–G but no anticoagulation was 5.6 months. Therefore, patients receiving tinzaparin had 39.54% higher PFS than patients without thromboprophylaxis (p < 0.05). During the follow-up period of 18.3 ± 11.7 months, three (2.7%) thrombotic events were recorded while two clinically relevant non-major bleeding events occurred (1.9%). In conclusion, PFS in advanced PaC patients undergoing chemotherapy is positively impacted by anticoagulation. Thromboprophylaxis with tinzaparin in treatment dose is efficient and safe.