Treatment Of Gastrointestinal Cancer Research Articles

Role of Probiotics in the Prevention and Treatment of GIT Cancers: Updated Review

Cancer, one of the leading causes of death worldwide, has been the subject of extensive study by many researchers. Cancer is affected by both genetic and immune system factors in the human body. The gut microbiota plays an important role in the body's capacity to maintain homeostasis. Because of their beneficial effects on human health and their ability to successfully prevent and treat various chronic diseases, such as cancer, probiotics are becoming increasingly important in medicine. A wealth of research has shown that probiotic consumption can significantly helpful in cancer prevention and treatment. The goal of this review is to provide a thorough overview of the research on the function of probiotic bacteria in the prevention and treatment of gastrointestinal cancers.

Abstract 1661: Heart-sparing ALK5 inhibitor for treatment of gastrointestinal and liver cancers

Abstract Transforming growth factor beta (TGFβ) signaling has been implicated in many cancers and fibrotic diseases. Recent pharmacological intervention has shown promising activities in preclinical models and early clinical trials. There are over 15 investigational agents targeting this pathway currently in the clinic, but none have been approved. In particular, small molecule TGFβ inhibitors targeting ALK5 (TGFβ type 1 receptor) have been limited by mechanism-based heart valve toxicity to low dose and intermittent dosing regimens. NEX002 is an oral liver-targeted ALK5 inhibitor with low heart exposure for the treatment of liver cancer and other gastrointestinal cancers with liver metastases. The compound was designed following drug design principles from known liver-specific drugs, such as the statins. In animals, NEX002 exerts preferential distribution (pharmacokinetic) and target inhibition (pharmacodynamic) in liver over the heart. NEX002 has demonstrated activity in several intrahepatic and subcutaneous tumor models, and significantly enhanced the durability of anti-tumor efficacy in combination with lenvatinib, a VEGFR inhibitor approved for the treatment of hepatocellular carcinoma. No heart valve toxicity was observed when benchmarked against galunisertib (systemic ALK5 inhibitor) in toxicity studies with repeated daily dosing. These data suggest that our liver-targeted/heart-sparing approach may allow more robust target engagement compared to systemic ALK5 inhibitors through higher dose or more frequent dosing. Citation Format: Andrew T. Miller, Qihui Jin, David Plouffe, Manny Corpuz, Evelyn Rodrigo, Tom Y.- Wu. Heart-sparing ALK5 inhibitor for treatment of gastrointestinal and liver cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1661.

Prehabilitation Before Gastrointestinal Cancer Surgery: Protocol for an Implementation Study.

Surgery remains the standard curative treatment for early-stage colorectal and upper gastrointestinal cancer. Reduced preoperative functional capacity, nutritional status, and psychological well-being are associated with poor postoperative outcomes. Prehabilitation aims to improve preoperative functional reserves through physical, nutritional, and psychological interventions. Yet, how it transitions from a trial setting to being integrated into a real-world health setting is unknown. The primary aim is to evaluate the implementation of a multimodal (supervised exercise, nutrition, and nursing support) prehabilitation program into standard care for patients with gastrointestinal cancer (colorectal and upper gastrointestinal cancer) scheduled for curative intent surgery. The secondary aim is to determine the impact of a multimodal prehabilitation program on functional capacity, nutritional and psychological status, and surgical outcomes. This is an implementation study that will investigate a multimodal prehabilitation intervention, in a nonblinded, nonrandomized, single-group, pre-post design. Patients diagnosed with colorectal and upper gastrointestinal cancer scheduled for potentially curative intent surgery at Concord Repatriation General Hospital, with ≥14 intervention days prior to surgery and are medically cleared to exercise will be eligible. The study will be evaluated using the Reach, Effectiveness, Adoption, Implementation, and Maintenance Evaluation Framework. The protocol was approved in December 2019 by the Concord Repatriation General Hospital Human Research Ethics Committee (reference number 2019/PID13679). Recruitment commenced in January 2020. In response to the COVID-19 pandemic, recruitment was paused in March 2020 and reopened in August 2020 with remote or telehealth intervention adaptations. Recruitment ended on December 31, 2021. Over the 16-month recruitment period, a total of 77 participants were recruited. Prehabilitation represents an opportunity to maximize functional capacity and improve surgical outcomes. The study will provide guidance and contribute to the evidence on the integration of prehabilitation into standard care using adaptive models of health care delivery including telehealth. Australian and New Zealand Clinical Trials Registry ACTR 12620000409976; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378974&isReview=true. RR1-10.2196/41101.

Heat shock protein 90 (HSP90) inhibitors in gastrointestinal cancer: where do we currently stand?-A systematic review.

Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers. We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease. Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors. It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.

Peroxisome proliferator-activated receptors regulate the progression and treatment of gastrointestinal cancers.

Peroxisome proliferator-activated receptors (PPARs) are essential nuclear hormone receptors regulating metabolic processes, and they participate in the initiation and progression processes of tumors. Gastrointestinal (GI) cancer is a prevalent malignancy worldwide that originates from the tissues of the gastrointestinal tract and is characterized by severe symptoms and poor prognosis. Numerous published studies have investigated the critical role of PPARs in esophageal, gastric, and colorectal cancers. Here, we summarize and review the current literature to understand the role of PPARs in the pathogenesis of GI cancers and to provide a systematic reference for the subsequent investigation and development of efficient therapies targeting PPARs and their pathways.

Intestinal Microbiomes In Gastrointestinal Cancer

The intestinal flora, a crucial system of microorganisms in the human body, is crucial to the immune system, metabolism, and inflammatory response of the body. The intestinal flora is one of them, and as a crucial element of the gastrointestinal microecology, it has a significant impact on the development and spread of gastrointestinal cancer as well as its management. The study of intestinal flora has become more in-depth recently as a result of the quick advancement of high-throughput sequencing technology, and the role of intestinal flora in the development and prognosis of gastrointestinal cancer is becoming increasingly obvious. In this article, the key topics covered include the links between Helicobacter pylori and gastric cancer, as well as the relationship between Fusobacterium and colon cancer, and discusses the mechanism by which intestinal microbes affect the treatment of gastrointestinal cancer. The link between gut microbiota and gastrointestinal cancer was further clarified, and the regulation of gut microbiota was proposed as a new management method for the clinical gastrointestinal cancer treatment.

Defect engineering endows NiTi stents with photothermal-enhanced catalytic activity for high-efficiency tumor therapy

NiTi stents are widely used in clinic for palliative care to relieve obstruction caused by Gastrointestinal (GI) cancers, which have high morbidity and mortality rates. However, tumor invasion and tumor overgrowth around the stent after surgery may lead to re-obstruction of the lumen. Thus, it is urgent to endow NiTi stents with excellent tumor suppressive ability and good biocompatibility. In this study, Ce-BTC was firstly prepared on the surface of NiTi pretreated by alkaline heat, followed by pyrolysis in Ar atmosphere at 450 °C. Then, a composite coating consisting of defective cerium oxide and black Ni-Ti hydroxide/oxide was constructed on NiTi surface, which exhibited tumor microenvironment-response and hyperthermia-enhanced catalytic ability. Under near-infrared light irradiation, the photothermal performance of black Ni-Ti hydroxide/oxide and hyperthermia-enhanced catalytic activity of defective cerium oxide can achieve a synergistic effect of photothermal therapy and tumor catalytic therapy. Thereafter, defective cerium oxide can sustainably inhibit the proliferation of residual tumor cells by the generation of reactive oxygen species. Moreover, the composite coating has no obvious cytotoxicity to normal cells. This work provides a new insight for the preparation of stimulus-responsive antitumor stents for palliative treatment of gastrointestinal cancer.

Is it feasible and ethical to randomize patients between surgery and non-surgical treatments for gastrointestinal cancers?

In several settings in the treatment of gastrointestinal cancers, it is unclear if the addition of surgery to a multimodal treatment strategy, or in some circumstances its omission, lead to a better outcome for patients. In such situations of clinical equipoise, high-quality evidence from randomised-controlled trials is needed to decide which treatment approach is preferable. In this article, we outline the importance of randomised trials comparing surgery with non-surgical therapies for specific scenarios in the treatment of gastrointestinal cancers. We explain the difficulties and solutions of designing these trials and recruiting patients in this context. We performed a selective review based on a not systematic literature search in core databases, supplemented by browsing health information journals and citation searching. Only articles in English were selected. Based on this search, we discuss the results and methodological characteristics of several trials which randomised patients with gastrointestinal cancers between surgery and non-surgical treatments, highlighting their differences, advantages, and limitations. Innovative and effective cancer treatment requires randomised trials, also comparing surgery and non-surgical treatments for defined scenarios in the treatment of gastrointestinal malignancies. Nevertheless, potential obstacles to designing and carrying out these trials must be recognised ahead of time to avoid problems before or during the trial.

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.

An optimized IgG-based B7-H3xCD3 bispecific antibody for treatment of gastrointestinal cancers

T cell-based immunotherapy has revolutionized oncological treatment. However, many patients do not respond to treatment, and long-term remissions remain rare, particularly in gastrointestinal cancers like colorectal cancer (CRC). B7-H3 is overexpressed in multiple cancer entities including CRC on both tumor cells and tumor vasculature, the latter facilitating influx of effector cells into the tumor site upon therapeutic targeting. We generated a panel of Tcell-recruiting B7-H3xCD3 bispecific antibodies (bsAbs) and show that targeting a membrane-proximal B7-H3 epitope allows for a 100-fold reduction of CD3 affinity. Invitro, our lead compound CC-3 showed superior tumor cell killing, Tcell activation, proliferation, and memory formation, whereas undesired cytokine release was reduced. Invivo, CC-3 mediated potent antitumor activity in three independent models using immunocompromised mice adoptively transferred with human effector cells with regard to prevention of lung metastasis and flank tumor growth as well as elimination of large established tumors. Thus, fine-tuning of both target and CD3 affinities as well as binding epitopes allowed for the generation of a B7-H3xCD3 bsAbs with promising therapeutic activity. CC-3 is presently undergoing good manufacturing practice (GMP) production to enable evaluation in a clinical "first-in-human" study in CRC.

Exosomal LncRNAs in Gastrointestinal Cancer: Biological Functions and Emerging Clinical Applications.

Due to the lack of specific and effective biomarkers and therapeutic targets, the early diagnosis and treatment of gastrointestinal cancer remain unsatisfactory. As a type of nanosized vesicles derived from living cells, exosomes mediate cell-to-cell communication by transporting bioactive molecules, thus participating in the regulation of many pathophysiological processes. Recent evidence has revealed that several long non-coding RNAs (lncRNAs) are enriched in exosomes. Exosomes-mediated lncRNAs delivery is critically involved in various aspects of gastrointestinal cancer progression, such as tumor proliferation, metastasis, angiogenesis, stemness, immune microenvironment, and drug resistance. Exosomal lncRNAs represent promising candidates to act as the diagnosis biomarkers and anti-tumor targets. This review introduces the major characteristics of exosomes and lncRNAs and describes the biological functions of exosomal lncRNAs in gastrointestinal cancer development. The preclinical studies on using exosomal lncRNAs to monitor and treat gastrointestinal cancer are also discussed, and the opportunities and challenges for translating them into clinical practice are evaluated.

Comparison of efficacy and safety between endoscopic mucosal dissection and resection in the treatment of early gastrointestinal cancer and precancerous lesions: a systematic review and meta-analysis.

Endoscopic mucosal dissection (EMD) is a new treatment method. Whether its clinical efficacy and safety are superior to surgical resection is still controversial. The sample size of previous studies on EMD for the treatment of early cancer of digestive tract is small, and there is no reliable evidence at present. Therefore, it is necessary to evaluate the efficacy and safety of EMD based on the evidence of evidence-based medicine. The PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, cqvip.com (VIP), websites and citation searching were searched to obtain relevant literature on EMD for early cancer and precancerous lesions of digestive tract. The retrieval time was from the establishment of the database to November 29th, 2022. Literature was screened according to inclusion and exclusion criteria and data and data were extracted. The final included literature was assessed by Cochrane risk of bias tool, and publication bias was assessed by Egger's test. A total of 10 articles were included, with a total of 1,165 patients. Among these, 585 cases were treated with EMD and 580 cases were in the control group. The literature quality evaluation found that 5 articles had low risk of bias and 5 articles had unclear risk of bias. The results showed that the complete resection rate in the observation group was higher than that in the control group [risk ratio (RR) =1.25, 95% confidence interval (CI): 1.15-1.35, P<0.01]. Cumulative intraoperative blood loss (P<0.01), operation time (P<0.01), postoperative complications (P<0.01), hospital stay (P<0.01), and hospitalization expenses (P<0.01) in the observation group were lower than those in the control group. EMD for early gastrointestinal cancer and precancerous lesions can improve the complete resection rate of tumors; reduce intraoperative blood loss, complications, operation time, and hospitalization time and cost. However, due to the small number of literatures included in this paper, the quality of literatures is not high, and some results have heterogeneous interference, the conclusion needs to include more high-treatment studies for further study.

Underutilization of fertility preservation discussions in reproductive age women undergoing treatment of advanced gastrointestinal (GI) cancers

Underutilization of fertility preservation discussions in reproductive age women undergoing treatment of advanced gastrointestinal (GI) cancers

PROPERTY: study protocol for a randomized, double-blind, multicenter placebo-controlled trial assessing neurotoxicity in patients with metastatic gastrointestinal cancer taking PHYCOCARE® during oxaliplatin-based chemotherapy

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse effects of antineoplastic agents, ranging in prevalence from 19% to over 85%. Clinically, CIPN is a predominantly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. The high prevalence of CIPN among cancer patients makes it a major problem for both patients and survivors, as well as for their health care providers, especially because there is currently no single effective method of preventing CIPN; moreover, the options for treating this syndrome are very limited.Phycocyanin, a biliprotein pigment and an important constituent of the blue-green algae Spirulina platensis, has been reported to possess significant antioxidant and radical-scavenging properties, offering protection against oxidative stress, which is one of the hypothetic mechanisms, between others, of CIPN occurrence.MethodsOur hypothesis is that phycocyanin may give protection against oxaliplatin-induced neuropathy in the treatment of gastrointestinal cancers. Our trial will be a randomized double-blind placebo-controlled study with 110 randomized patients suffering from metastatic gastrointestinal adenocarcinoma including esogastric, colorectal, and pancreatic cancers. Patients are being followed up in the gastroenterology or oncology departments of seven French hospitals.DiscussionDue to the neuropathy, patients need to avoid injury by paying careful attention to home safety; patients’ physicians often prescribe over-the-counter pain medications. If validated, our hypothesis should help to limit neurotoxicity without the need to discontinue chemotherapy.Trial registrationClinicalTrials.gov NCT05025826. First published on August 27, 2021.

A review of hydrogels used in endoscopic submucosal dissection for intraoperative submucosal cushions and postoperative management.

Endoscopic submucosal dissection (ESD) has been clinically proved to have prominent advantages in the treatment of early gastrointestinal cancers over traditional surgery, including less trauma, fewer complications, a quicker recovery and lower costs. During the procedure of ESD, appropriate and multifunctional submucosal injected materials (SIMs) as submucosal cushions play an important role, however, even with many advances in design strategies of SIMs over the past decades, the performance of the submucosal cushions with postoperative management function seems to be still unsatisfactory. In this review, we gave a brief historical recount about the clinical development of SIMs, then some common applications of hydrogels used as SIMs in ESD were summarized, while an account of the universal challenges during ESD procedure was also outlined. Going one step further, some cutting-edge functional strategies of hydrogels for novel applications in ESD were exhibited. Finally, we concluded the advantages of hydrogels as SIMs for ESD as well as the treatment dilemma clinicians faced when it comes to deeply infiltrated lesions, some technical perspectives about linking the clinical demand with commercial supply were also proposed. Encompassing the basic elements of SIMs used in ESD surgery and the corresponding postoperative management requirements, this review could be a good reference for relevant practitioners in expanding the research horizon and improving the well-being index of patients.

Application and Future Prospects of Intraoperative Fluorescence Imaging in The Treatment of Gastrointestinal Cancer

消化管癌治療における蛍光イメージングには，indocyanine green蛍光を用いた血流評価，センチネルノード（SN）の検出や，近赤外蛍光クリップ，腫瘍の蛍光ラベル等がある．血流評価は左側大腸での評価が進みつつある．SNは胃癌において時間をかけながらポジティブなな結果が積み重なってきている．さらに，近赤外蛍光樹脂を用いたクリップなどのデバイス開発や腫瘍を蛍光ラベルする試みが具体化しつつある．

Venous thromboembolism (VTE) in gastrointestinal cancer treatment

Venous thromboembolism (VTE) in gastrointestinal cancer treatment

Incorporation of Combination Immunotherapy into the Treatment Paradigms of Gastrointestinal Cancers

Immune checkpoint inhibitors allow innate immune cells to recognize and attack tumour cells by removing inhibitory signals associated with tumours and their microenvironment. These agents can induce durable responses and they have transformed the management of many cancer types. There have been great efforts to incorporate immunotherapy (IO) into the treatment of gastrointestinal (GI) cancers. However, most of the GI cancers, except for microsatellite unstable tumours, are largely resistant to IO, especially when used as monotherapy. Increased efficacy has been observed when these agents are combined with other drugs, including chemotherapy, other immune checkpoint inhibitors, or targeted drugs. This review will summarize recent advances in the management of GI cancers with the incorporation of immune checkpoint inhibitors into current treatment paradigms. It will review pivotal studies that led to these practice updates and highlight potentially practice-changing ongoing clinical studies that involve IO agents.

Clinical Outcomes of Comprehensive Genomic Profiling Tests for Gastrointestinal Cancers: Experience from Tokushima University Hospital

In Japan, cancer genome profiling (CGP) for cancer patients without standard treatment has been covered by public insurance since June 2019. This study analyzed data of 122 patients with gastrointestinal tumors who underwent CGP to clarify cancer genome medicine's current status and possible problems at the Tokushima University Hospital. The major types of cancer included pancreatic (n=30), colorectal (n=25), biliary tract (n=15), gastric (n=11), and hepatocellular carcinoma (n=8). CGP tests included F1CDx in 70 patients (57%), F1LCDx in 36 (30%), TSO500 in 14 (11%), and NCC Oncopanel in 2 (2%). Actionable gene alterations were identified in 72 patients (59%), but only 5 patients (4%) were treated for pancreatic (n=1), colorectal (n=3), and small bowel cancers (n=1). The main reasons for not receiving genotype-matched therapy included the lack of appropriate drugs or clinical trials that matched the actionable gene alterations (n=40) and the inability to participate in clinical trials (n=10). There is still not a sufficient number of patients receiving genotype-matched treatment for gastrointestinal cancers. To promote cancer genome medicine in regional areas, attempts to improve access to genotype-matched therapies are required, as well as to promote the development of new molecular-targeted drugs and clinical trials for these drugs. J. Med. Invest. 70 : 154-159, February, 2023.