Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates around 10%. The only curative option remains complete surgical resection, but due to the delay in diagnosis, less than 20% of patients are eligible for surgery. Therefore, discovering diagnostic biomarkers for early detection is crucial for improving clinical outcomes. Metabolomics has become a powerful technology for biomarker discovery, and several metabolomic-based panels have been proposed for PDAC diagnosis, but these advances have not yet been translated into the clinic. Therefore, this review focused on summarizing metabolites identified for the early diagnosis of PDAC in the last five years. Bibliographic searches were performed in the PubMed, Scopus and WOS databases, using the terms “Biomarkers, Tumor”, “Pancreatic Neoplasms”, “Early Diagnosis”, “Metabolomics” and “Lipidome” (January 2018–March 2023), and resulted in the selection of fourteen original studies that compared PDAC patients with subjects with other pancreatic diseases. These investigations showed amino acid and lipid metabolic pathways as the most commonly altered, reflecting their potential for biomarker research. Furthermore, other relevant metabolites such as glucose and lactate were detected in the pancreas tissue and body fluids from PDAC patients. Our results suggest that the use of metabolomics remains a robust approach to improve the early diagnosis of PDAC. However, these studies showed heterogeneity with respect to the metabolomics techniques used and further studies will be needed to validate the clinical utility of these biomarkers.

Recently, invertebrate marine species have been investigated for the presence of natural products with antitumor activity. We analyzed the invertebrate Anemonia sulcata with (W) and without (W/O) the presence of its microalgal symbiont Symbiodinium as a source of bioactive compounds that may be applied in the therapy and/or prevention of colorectal cancer (CRC). Animals were mechanically homogenized and subjected to ethanolic extraction. The proximate composition and fatty acid profile were determined. In addition, an in vitro digestion was performed to study the potentially dialyzable fraction. The antioxidant and antitumor activity of the samples and the digestion products were analyzed in CRC cells in vitro. Our results show a high concentration of polyunsaturated fatty acid in the anemone and a great antioxidant capacity, which demonstrated the ability to prevent cell death and a high antitumor activity of the crude homogenates against CRC cells and multicellular tumor spheroids, especially W/O symbiont. These preliminary results support that Anemonia sulcata could be a source of bioactive compounds with antioxidant and antitumor potential against CRC and that the absence of its symbiont may enhance these properties. Further studies will be necessary to define the bioactive compounds of Anemonia sulcata and their mechanisms of action.

Multidrug resistance (MDR) development against cytotoxic drugs by tumor cells is one of the main causes of treatment failure in gastrointestinal cancers, a group of cancers of great relevance due to their prevalence and/or mortality. This phenomenon is mediated by diverse mechanisms, including the overexpression of members of the superfamily of membrane transporters of the ATP-binding cassette (ABC). Most of these molecules, including P-glycoprotein (P-gp or MDR1/ABCB), MDR-associated protein 1 (MRP1/ABCC1), MRP2, and breast cancer resistance protein (BCRP/ABCG2), are integrated in the cell membrane, acting as drug efflux pumps. Despite the use of various MDR modulators as adjuvants to improve the chemotherapy response, the results have not been satisfactory. Natural products from plants, such as flavonoids, alkaloids, terpenoids, and coumarins, are capable of modifying drug resistance, suggesting an improvement in the antitumoral effect of the current treatments without generating side effects. This review aims to provide an overview of the most recent studies in relation to plant-derived molecules and extracts that modulate resistance to antitumor drugs and that could be applied in the future in clinical practice to improve the treatment of patients with gastrointestinal cancer.

Anemonia sulcata may be a source of marine natural products (MNPs) due to the antioxidant and antitumor activity of its crude homogenates shown in vitro in colon cancer cells. A bioguided chromatographic fractionation assay of crude Anemonia sulcata homogenates with and without its symbiont Symbiodinium was performed to characterize their bioactive composition and further determine their biological potential for the management of colorectal cancer (CRC). The 20% fractions retained the in vitro antioxidant activity previously reported for homogenates. As such, activation of antioxidant and detoxifying enzymes was also evaluated. The 40% fractions showed the greatest antiproliferative activity in T84 cells, synergistic effects with 5-fluoruracil and oxaliplatin, overexpression of apoptosis-related proteins, cytotoxicity on tumorspheres, and antiangiogenic activity. The predominantly polar lipids and toxins tentatively identified in the 20% and 40% fractions could be related to their biological activity in colon cancer cells although further characterizations of the active fractions are necessary to isolate and purify the bioactive compounds.

Background. Worldwide, colorectal cancer is the third most commonly diagnosed cancer. It is the second leading cause of cancer-related mortality. Recent studies establish a relationship between natural compounds from plants with the prevention and treatment of cancer. Specifically, glucosinolates with antitumoral capacity and polyphenols with the ability to scavenge free radicals that can cause cell damage have been identified in the Brassicaceae family. Objectives. Based on the previously mentioned factors, this study aimed to develop a nutraceutical made with extracts from different Brassicaceae seeds and study its antioxidant and antiproliferative action in vitro and in vivo using the AOM/DSS model in CC57BL6J mice. Results. Extract from the seeds of Eruca sativa and Sinapis alba showed the highest antioxidant capacity among the different species studied and were selected for nutraceutical formulation, which was potentially absorbable (73%) after an in vitro digestion process. In total, thirty compounds were identified in the nutraceutical that could be responsible for its antioxidant and tumoral prevention capacity. The intake of nutraceutical was a successful intervention to prevent the development of polyps by 31.6% and their size by 53.9%. When the nutritional intervention was used in combination with a physical exercise protocol, these parameters dropped to 52.3% and 62.6%, respectively. Conclusions. These findings suggest that the consumption of a diet rich in bioactive compounds from Brassica species, in combination with physical activity, is a valuable prevention strategy for colorectal cancer. However, more research is required to evaluate the efficacy and safety of these interventions in clinical settings.