Therapy For Gastrointestinal Cancers Research Articles

1060P Balance of CD36+ and CD16+ monocytes controls TLR-mediated cytokine release syndrome and MHC-dependent antitumor responses in EpCAM CAR T cell therapy for gastrointestinal cancers

1060P Balance of CD36+ and CD16+ monocytes controls TLR-mediated cytokine release syndrome and MHC-dependent antitumor responses in EpCAM CAR T cell therapy for gastrointestinal cancers

Manganese-based nanoparticles for chemodynamic therapy of gastrointestinal cancer

To investigate the physicochemical features of glucose oxidase-loaded and manganese-based mesoporous silica nanoparticles (MSN@Mn-GOx) and its antitumor effect against gastrointestinal cancer. The morphology, particle size and Fenton-like properties of MSN@Mn-GOx nanoparticles were analyzed using transmission electron microscopy (TEM), dynamic light scattering (DLS), Zeta potential analysis, ultraviolet absorption spectroscopy, energy dispersive spectroscopy and X-ray photoelectron spectroscopy. A mouse model bearing human colon cancer HT-29 xenograft was established to examine the antitumor effect of MSN@Mn-GOx using MRI imaging. Reactive oxygen species (ROS) production assay, CCK-8 assay and EdU assay were used to evaluate the in vitro anti-tumor effect of the nanoparticles. MSN@Mn-GOx nanoparticles were solid spheres with a diameter of about 100 nm and a Zeta potential of -35 mV. MSN@Mn-GOx had a higher H2O2 catalytic efficiency in glucose containing solution than in glucose-free solution, and showed a stronger Fenton-like properties at pH6.0 than at pH7.4 (P＜0.05). In the tumor-bearing mice, MSN@Mn-GOx treatment dose-dependently enhanced T1 imaging of the tumor (P＜0.01). Compared with the control group and MSN@Mn group, MSN@Mn-GOx induced a significantly higher level of ROS production and a stronger inhibitory effect on the proliferation of gastric and colon cancer cells (P＜0.05). MSN@Mn-GOx nanoparticles have good chemodynamic properties and a strong anti-tumor effect and provide a potential therapeutic option for gastric cancer.

Bioenergetic alteration in gastrointestinal cancers: The good, the bad and the ugly.

Cancer cells exhibit metabolic reprogramming and bioenergetic alteration, utilizing glucose fermentation for energy production, known as the Warburg effect. However, there are a lack of comprehensive reviews summarizing the metabolic reprogramming, bioenergetic alteration, and their oncogenetic links in gastrointestinal (GI) cancers. Furthermore, the efficacy and treatment potential of emerging anticancer drugs targeting these alterations in GI cancers require further evaluation. This review highlights the interplay between aerobic glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS) in cancer cells, as well as hypotheses on the molecular mechanisms that trigger this alteration. The role of hypoxia-inducible transcription factors, tumor suppressors, and the oncogenetic link between hypoxia-related enzymes, bioenergetic changes, and GI cancer are also discussed. This review emphasizes the potential of targeting bioenergetic regulators for anti-cancer therapy, particularly for GI cancers. Emphasizing the potential of targeting bioenergetic regulators for GI cancer therapy, the review categorizes these regulators into aerobic glycolysis/ lactate biosynthesis/transportation and TCA cycle/coupled OXPHOS. We also detail various anti-cancer drugs and strategies that have produced pre-clinical and/or clinical evidence in treating GI cancers, as well as the challenges posed by these drugs. Here we highlight that understanding dysregulated cancer cell bioenergetics is critical for effective treatments, although the diverse metabolic patterns present challenges for targeted therapies. Further research is needed to comprehend the specific mechanisms of inhibiting bioenergetic enzymes, address side effects, and leverage high-throughput multi-omics and spatial omics to gain insights into cancer cell heterogeneity for targeted bioenergetic therapies.

Combination of Immunotherapy and Radiation Therapy in Gastrointestinal Cancers: An Appraisal of the Current Literature and Ongoing Research.

Oncological outcomes are improving in gastrointestinal cancer with advancements in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT) to allow for further improvements. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. A few recent phase III studies have shown improved survival with the addition of immunotherapy to standard treatment for gastrointestinal cancer. The timing, duration, sequencing, and integration with other anti-cancer treatments are still areas of ongoing research. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

Altered expression of AXL receptor tyrosine kinase in gastrointestinal cancers: a promising therapeutic target.

Gastrointestinal (GI) cancers that include all cancers of the digestive tract organs are generally associated with obesity, lack of exercising, smoking, poor diet, and heavy alcohol consumption. Treatment of GI cancers typically involves surgery followed by chemotherapy and/or radiation. Unfortunately, intrinsic or acquired resistance to these therapies underscore the need for more effective targeted therapies that have been proven in other malignancies. The aggressive features of GI cancers share distinct signaling pathways that are connected to each other by the overexpression and activation of AXL receptor tyrosine kinase. Several preclinical and clinical studies involving anti-AXL antibodies and small molecule AXL kinase inhibitors to test their efficacy in solid tumors, including GI cancers, have been recently carried out. Therefore, AXL may be a promising therapeutic target for overcoming the shortcomings of standard therapies in GI cancers.

Repetitive presentations of phase II and III trials involving systemic therapies in gastrointestinal (GI) malignancies at international meetings in the past few years.

e18638 Background: The American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) annual meetings as well as their GI dedicated meetings (ASCO GI and ESMO GI) have the premise to accept abstracts for oral presentations that have not been previously presented. Methods: We conducted a review of all 220 abstracts involving phase II or III trials of systemic therapies that have been presented orally from June 2019 to January 2023 at ASCO, ASCO GI, ESMO and ESMO GI meetings to evaluate the incidenceof repetitive presentations of the same trial in different meetings as well as their relationship to pharmaceutical industry sponsorship. ANOVA test was used to compare means between different groups and p values of ≤ 0.1 were considered significant. Results: Overall, 20,9% of accepted oral abstracts from phase II or III trials were replicated during the 4-year time frame. Of them, 39% were phase II, 61% phase III, 72% pharma sponsored, 39% included developing countries, and 59% were positive. The association of industry sponsorship and study positivity indicated a variation of up 3,55 appearances (p 0,017) in the number of times this research was orally presented. Conclusions: Our findings suggest that almost 20% of oral abstracts involving systemic therapies in GI cancers are presented more than once at relevant meetings, especially those with positive results and sponsored by pharma. Our study highlights the need for a more effective oral abstract selection system in oncology meetings.

Antimicrobial peptides as potential therapy for gastrointestinal cancers.

Since conventional therapy faces limitations in the field of different cancers as well as gastrointestinal cancers, that decrease the survival rate of patients, there is an urgent need to find new effective therapeutic approaches without the adverse effects of the traditional agents. Antimicrobial peptides (AMPs) attract much attention and are well known for their role in innate immunity. These peptides, in addition to their antimicrobial activity, exhibit strong anticancer potential against various types of malignancy. AMPs specifically target tumor cells and have selective toxicity for these cells without affecting normal cells. Here we aim to comprehensively overview the current knowledge in the field of using AMPs as novel therapeutic agents for gastrointestinal cancer.

A strategy for the treatment of gastrointestinal cancer: Targeting tumor senescent cells.

Gastrointestinal (GI) cancer includes a variety of cancers with high incidence that seriously threaten the lives of people worldwide. Although treatment strategies continue to improve, patient benefits are still very limited, and the ongoing search for new treatment strategies remains a priority. Cell senescence is closely related to the occurrence and development of tumors. For GI cancer, cell senescence may not only promote cancer but also bring new opportunities for treatment. Combined with relevant studies, we review the dual role of cell senescence in GI cancer, including the mechanism of inducing cell senescence, biomarkers of senescent cells, and potential of targeted senescence therapy for GI cancer.

Research progress of potential factors influencing photodynamic therapy for gastrointestinal cancer.

Gastrointestinal cancer is a malignant tumor of the gastrointestinal tract and its associated digestive organs, including esophageal cancer, gastric cancer, carcinoma of the ampulla, pancreas, bile duct, intestines and rectal cancer. They account for about 30% of global cancer-related incidence and about 40% of mortality. Photodynamic therapy (PDT), as a treatment mode, has been applied to the treatment of gastrointestinal cancer due to potential advantages targeting and potentially lower toxic side effects. However, In the course of clinical treatment, we have found that different patients have various responsiveness to PDT, and even the same patients may have different clinical effects after receiving treatment in different time periods. For influencing factors, traditionally, we only focus on adjusting the dose of photosensitizer and the intensity and time of irradiation,while minimizing other potential factors.Therefore, this paper looks for factors that affect PDT from the patient's own conditions, tumor characteristics and tumor microenvironment(including:tumor acidic microenvironment,tumor hypoxic microenvironment, multi-drug resistance, different tumor characteristics and the immune status of patients) and summarizes how to potentially improve the curative effect of PDT.

Targeting lipid metabolism with natural products: A novel strategy for gastrointestinal cancer therapy.

Gastrointestinal cancer (GIC), including gastric cancer and colorectal cancer, is a common malignant tumor originating from gastrointestinal epithelial cells. Although the pathogenesis of GIC remains unclear, aberrant lipid metabolism has emerged as a hallmark of cancer. Several enzymes, proteins, and transcription factors are involved in lipid metabolism reprogramming in GIC, and their abnormal expression can promote lipid synthesis and accumulation of lipid droplets through numerous mechanisms, thereby affecting the growth, proliferation, and metastasis of GIC cells. Studies show that some natural compounds, including flavonoids, alkaloids, and saponins, can inhibit the de novo synthesis of lipids in GIC, reduce the level of lipid accumulation, and subsequently, inhibit the occurrence and development of GIC by regulating Sterol regulatory element-binding protein 1 (SREBP-1), adenosine monophosphate-activated protein kinase (AMPK), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), phosphatidylinositol-3-kinase/Akt and the mammalian target of rapamycin PI3K/Akt/mTOR, amongst other targets and pathways. Therefore, targeting tumor lipid metabolism is the focus of anti-gastrointestinal tumor therapy. Although most natural products require further high-quality studies to firmly establish their clinical efficacy, we review the potential of natural products in the treatment of GIC and summarize the application prospect of lipid metabolism as a new target for the treatment of GIC, hoping to provide a reference for drug development for gastrointestinal tumors.

A prospective translational study investigating the association of gut microbiome (GM) diversity with pathological complete response (pCR) after neoadjuvant treatment in early stage rectal and esophageal cancers.

TPS819 Background: The gut microbiome (GM) is thought to influence host immunity by modulating multiple immunologic pathways. Studies have suggested that dysbiosis of the GM confers a predisposition to certain malignancies and influences response to immune checkpoint inhibitors. However, little is known about how the GM diversity influences complete pathological response to neoadjuvant therapy in gastrointestinal (GI) tumours. We hypothesize that a more diverse GM constitution at baseline will lead to improved pathological response at the time of definitive surgery. Methods: We designed a cross-institutional multi-center translational study investigating the impact of the GM diversity on the efficacy of neoadjuvant therapy in GI cancers by assessing its association with pathological response. The study population will consist of patients with an early-stage rectal or esophageal cancer due to commence neoadjuvant therapy (including chemotherapy and chemoradiation) and planned for definitive surgery. Patients who received prior chemotherapy/monoclonal antibodies/immune checkpoint inhibitors or radiation will be excluded. The study assessments will include fecal sampling of the GM prior to neoadjuvant therapy, upon completion and again six months post completion of therapy. Fecal samples will be analysed by 16S RNA sequencing. Pathological response will be examined at time of surgery and patients will be classified as responders (complete pathological response) or non-responders. The primary endpoint of the study is to examine the association between the GM diversity and pathological response. 120 patients will be recruited over 18 months. Results: Species richness (Alpha Diversity) will be analysed using the Shannon diversity index and Jaccard similarity index to calculate beta diversity. Classification and clustering analysis will be performed with Principal Component Analysis (PCA) and Random Forest analysis. Comparison of taxa or functions between clinical cohorts will be performed using the two tailed Z test and corrected using the false discovery rate to determine Q-values. The association between GM and complete pathological response will be examined using logistic regression analysis adjusting for potential confounding factors. Adjusted odds ratios (OR) and 95% confidence intervals will be presented. Conclusions: This study will show preliminary insights into the role of GM as a potential biomarker for neoadjuvant therapy efficacy in patients with GI cancers. Recruitment is on-going.

MR-linac based radiation therapy in gastrointestinal cancers: a narrative review.

Magnetic resonance guided radiotherapy (MRgRT) is an emerging technological innovation with more and more institutions gaining clinical experience in this new field of radiation oncology. The ability to better visualize both tumors and healthy tissues due to excellent soft tissue contrast combined with new possibilities regarding motion management and the capability of online adaptive radiotherapy might increase tumor control rates while potentially reducing the risk of radiation-induced toxicities. As conventional computed tomography (CT)-based image guidance methods are insufficient for adaptive workflows in abdominal tumors, MRgRT appears to be an optimal method for this tumor site. The aim of this narrative review is to outline the opportunities and challenges in magnetic resonance guided radiation therapy in gastrointestinal cancers. We searched for studies, reviews and conceptual articles, including the general technique of MRgRT and the specific utilization in gastrointestinal cancers, focusing on pancreatic cancer, liver metastases and primary liver cancer, rectal cancer and esophageal cancer. This review is highlighting the innovative approach of MRgRT in gastrointestinal cancer and gives an overview of the currently available literature with regard to clinical experiences and theoretical background. MRgRT is a promising new tool in radiation oncology, which can play off several of its beneficial features in the specific field of gastrointestinal cancers. However, clinical data is still scarce. Nevertheless, the available literature points out large potential for improvements regarding dose coverage and escalation as well as the reduction of dose exposure to critical organs at risk (OAR). Further prospective studies are needed to demonstrate the role of this innovative technology in gastrointestinal cancer management, in particular trials that randomly compare MRgRT with conventional CT-based image-guided radiotherapy (IGRT) would be of high value.

Potential Application of Small Interfering RNA in Gastro-Intestinal Tumors.

Despite the progress made in the diagnoses and therapy of gastrointestinal cancers, these diseases are still plagued by a high mortality. Thus, novel therapeutic approaches are urgently required. In this regard, small interfering RNA (siRNA), double-stranded RNA molecules able to specifically target the mRNA of pathological genes, have the potential to be of therapeutic value. To be effective in the human body, siRNAs need to be protected against degradation. Additionally, they need to target the tumor, leaving the normal tissue untouched in an effort to preserve organ function. To accomplish these tasks, siRNAs have been formulated with smart delivery systems such has polymers and lipids. While siRNA protection is not particularly difficult to achieve, their targeting of tumor cells remains problematic. Here, after introducing the general features of gastrointestinal cancers, we describe siRNA characteristics together with representative delivery systems developed for gastrointestinal cancers. Afterward, we present a selection of research papers employing siRNAs against upper- and lower- gastrointestinal cancers. For the liver, we also consider papers using siRNAs to combat liver cirrhosis, a relevant risk factor for liver cancer development. Finally, we present a brief description of clinical trials employing siRNAs for gastrointestinal cancers.

Nanocarriers for Active Ingredients of Chinese Medicine (AIFCM) Used in Gastrointestinal Cancer Therapy

Active ingredients of Chinese medicine (AIFCM) are pharmacological substances taken from traditional Chinese medicine that show promise in treating gastrointestinal cancer. Compared with traditional chemotherapeutic drugs, AIFCM have advantages such as multi-target and multi-level treatment of gastrointestinal cancer. Nanocarriers have the following advantages, better bioavailability, passive or active targeting of tumor sites and responsive release of drugs. The use of nanocarriers for delivery of AIFCM in treatment of gastrointestinal cancer, can overcome the disadvantages of some AIFCM, such as insolubility and low bioavailability. In this review, we first outline the background on gastrointestinal cancer, main curative factors and conventional therapeutic approaches. Then, the mechanisms for AIFCM in gastrointestinal cancer therapy are presented in the following four aspects: gene regulation, immune modulation, cellular pathway transduction, and alteration of intestinal flora. Thirdly, preparation of various nanocarriers and results when combining AIFCM in gastrointestinal cancer are presented. Fourth, application of novel targeted nanocarriers and responsive nanocarriers in gastrointestinal tumors is further introduced. Finally, the application of AIFCM in the treatment of gastrointestinal cancer is summarized and prospected, hoping to shed some light on the nanocarrier-bound AIFCM in the treatment of gastrointestinal cancer.

Targeting myeloid villains in the treatment with immune checkpoint inhibitors in gastrointestinal cancer.

Despite the clinical outcomes being extremely limited, blocking immune inhibitory checkpoint pathways has been in the spotlight as a promising strategy for treating gastrointestinal cancer. However, a distinct strategy for the successful treatment is obviously needed in the clinical settings. Myeloid cells, such as neutrophils, macrophages, dendritic cells, and mast cells, are the majority of cellular components in the human immune system, but have received relatively less attention for the practical implementation than T cells and NK cells in cancer therapy because of concentration of the interest in development of the immune checkpoint blocking antibody inhibitors (ICIs). Abnormality of myeloid cells must impact on the entire host, including immune responses, stromagenesis, and cancer cells, leading to refractory cancer. This implies that elimination and reprogramming of the tumor-supportive myeloid villains may be a breakthrough to efficiently induce potent anti-tumor immunity in cancer patients. In this review, we provide an overview of current situation of the IC-blocking therapy of gastrointestinal cancer, including gastric, colorectal, and esophageal cancers. Also, we highlight the possible oncoimmunological components involved in the mechanisms underlying the resistance to the ICI therapy, particularly focusing on myeloid cells, including unique subsets expressing IC molecules. A deeper understanding of the molecular and cellular determinants may facilitate its practical implementation of targeting myeloid villains, and improve the clinical outcomes in the ICI therapy of gastrointestinal cancer.

Correction to: Therapeutic potential of ginger bio-active compounds in gastrointestinal cancer therapy: the molecular mechanism

Correction to: Therapeutic potential of ginger bio-active compounds in gastrointestinal cancer therapy: the molecular mechanism

Therapeutic potential of ginger bio-active compounds in gastrointestinal cancer therapy: the molecular mechanism

Therapeutic potential of ginger bio-active compounds in gastrointestinal cancer therapy: the molecular mechanism

Pull the plug: Anti-angiogenesis potential of natural products in gastrointestinal cancer therapy.

Gastrointestinal cancer (GIC), including gastric cancer and colorectal cancer, is a common malignant tumor originating from the gastrointestinal epithelium. Although the pathogenesis of GIC has not been fully elucidated, angiogenesis is recognized as the key pathological basis for the growth, invasion and metastasis of cancer cells, and GIC angiogenesis is closely related to vascular endothelial growth factor family, hypoxia-inducible factor family, fibroblast growth factor family and matrix metalloproteinase family. Recently, many natural products have shown a wide range of pharmacological biological activities against GIC. In this review, the effects and mechanisms of natural compounds on the angiogenesis of gastric and colorectal cancer were summarized. The results show that some natural compounds, especially gallic catechin gallate, astragaloside and curcumin, can effectively inhibit angiogenesis; the HIF-1α/VEGF, COX-2/PGE2, HGF/c-Met and PI3K/Akt/mTOR are involved in these inhibition effects. This review examines the anti-angiogenesis potential of natural products in the GIC treatment and provides clues to the development of vascular targeted agents.

N-2-(Phenylamino) Benzamide Derivatives as Dual Inhibitors of COX-2 and Topo I Deter Gastrointestinal Cancers via Targeting Inflammation and Tumor Progression.

Given the close association between inflammation and cancer, combining anti-inflammation therapy is prominent to improve the anticancer effect. Based on I-1, a series of agents targeting COX-2 and Topo I were designed by combining fenamates and phenols. The optimal compound 1H-30 displayed an enhanced inhibitory effect on COX-2 compared to tolfenamic acid and I-1 and showed better inhibition of Topo I than I-1. Importantly, 1H-30 showed potential anticancer effects and suppressed the activation of the NF-κB pathway in cancer cells. 1H-30 inhibited the nuclear translocation of NF-κB and suppressed the production of NO, COX-2, and IL-1β in RAW264.7. In vivo, 1H-30 showed acceptable pharmacokinetic parameters, decreased the tumor growth without affecting the body weight, down-regulated COX-2 and MMP-9, and induced apoptosis in the CT26.WT tumor-bearing mice. Accordingly, 1H-30 as a potential Topo I/COX-2 inhibitor which possessed anti-inflammatory and anticancer effects, with inhibition of the NF-κB pathway, is promising for gastrointestinal cancer therapy.

Current State of Cell Therapies for Gastrointestinal Cancers.

Adoptive cell therapies include multiple cell-based therapies to harness the immune system's power to mount a robust anticancer effect. Early successes in solid tumors with checkpoint inhibition have increased the research and development of immunotherapy. The utilization of cell-based therapy for gastrointestinal malignancies is still in its infancy because of challenges of antigen specificity and access to the tumor microenvironment. In this review, we discuss the current state of adoptive cell therapies in terms of challenges and early successes in preclinical and clinical studies.