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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 int

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… Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): An open-label, multicentre, phase 2 study . … Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-Deficient/Microsatellite instability-high metastatic colorectal cancer . J Clin Oncol ( 2018 ) 36 ( 8 ): 773–9 . doi: 10.1200/JCO.2017.76.9901 29355075 64 Ashktorab H Ahuja S Kannan L Llor X Ellis NA Xicola RM . …

Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.

Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulat

Total Body Irradiation in Haematopoietic Stem Cell Transplantation: A Comprehensive Literature Review and Institutional Experience from the Policlinico of Catania.

Background and Objectives: Total body irradiation (TBI) remains a cornerstone of conditioning for allogeneic haematopoietic stem-cell transplantation (HSCT). Whereas early research debated the need for irradiation, contemporary investigations focus on optimising dose, fractionation and delivery techniques. Material and Methods: We synthesised six decades of evidence, spanning from single-fraction cobalt treatments to modern helical tomotherapy and intensity-modulated total-marrow/lymphoid irradiation (TMI/TMLI). To complement the literature, we reported our institutional experience on 77 paedi

DNA Damaging Drugs

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Keyword Index for Volume 111

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Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted t

CS-6-induced p62 accumulation exacerbates DNA damage in colorectal cancer.

BACKGROUND: Gamabufotalin (CS-6), a bufadienolide derived from Chansu, has been reported to exhibit anti-tumor effects in various cancers, including glioblastoma, nonsmall cell lung cancer, and breast cancer. However,its role in colorectal cancer (CRC) remains unexplored. OBJECTIVE: Our study aimed to evaluate the inhibition of CS-6 to CRC cells by cell viability assay, colony formation assay, comet assay, and cell cycle analysis firstly. And its molecular mechanism was studied by immunofluorescence (IF) assay, western blot (WB) assay, siRNA transfection, protein-protein interaction (PPI) net

Aging modulation of the immune system and immunotherapy efficacy in cancer.

Immunosenescence is characterized by immune decline and chronic inflammation. With advancing age, the incidence of tumors increases significantly. Understanding how immunosenescence influences the initiation and progression of tumors, as well as its implications for tumor immunotherapy, has become a matter of urgent importance. This review begins with an analysis of the phenotypic changes and underlying mechanisms associated with immune system and immune cell aging, and further explores the interplay between immunosenescence and tumorigenesis. Evidence indicates that cytokines, cell interactio

Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.

Cancer immunotherapy is a groundbreaking therapeutic strategy, yet it continues to face significant challenges, including limited overall response rates and treatment resistance. Emerging research has demonstrated the pivotal role of epigenetic modifications in tumor immune evasion, providing a strong rationale for developing "epi-immunotherapy"-an innovative approach that combines epigenetic therapy with immunotherapy. This comprehensive review systematically examines how epigenetic regulation mediates tumor immune escape and the mechanisms involved, including suppression of tumor antigen exp

Nature-Inspired Strategies in Cancer Management: The Potential of Plant Extracts in Modulating Tumour Biology.

Cancer is a serious group of diseases that is a huge problem on a global scale and is the second most common cause of death. Commonly used therapies do not always lead to the complete elimination of diseased cells or tissues and are also burdened with side effects that reduce the quality of life of patients. Due to these difficulties, new therapeutic approaches are still being sought. In recent years, there has been a return to interest in natural methods of treating various diseases, among which phytochemicals are particularly interesting. This article reviews plant extracts with anticancer p

The Role of Nucleotide Excision Repair in Cisplatin-Induced Peripheral Neuropathy: Mechanism, Prevention, and Treatment.

Platinum-based chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting effects of cancer treatment and results in dose reduction and discontinuation of life-saving chemotherapy. Its debilitating effects are often permanent and lead to lifelong impairment of quality of life in cancer patients. While the mechanisms underlying the toxicity are not yet fully defined, dorsal root ganglia sensory neurons play an integral role in symptom development. DNA-platinum adducts accumulate in these cells and inhibit normal cellular function. Nucleotide excision repair (NER)

Ixazomib decreases the risk of chronic graft-versus-host disease: identification of cGVHD biomarkers.

AbstractChronic graft-versus-host disease (cGVHD) is the leading cause of long-term morbidity and mortality after allogeneic hematopoietic stem cell transplantation. We hypothesize that it is possible to decrease its risk by manipulating the immune response in late phases of transplantation. We performed a prospective randomized trial including 73 patients. Patients in the treatment arm received 4 mg of ixazomib (IXZ) every 28 days from day +100. With a median follow-up of 24 months, the cumulative incidence of moderate/severe cGVHD in the IXZ vs control groups at 1 and 2 years were: 3.23% vs

Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation.

Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence

Recent advances in precision oncology research.

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NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance.

Neurotrophic tropomyosin receptor kinase (NTRK) gene fusion has been identified as an oncogenic driver of various solid tumors, and it is rare in non-smalll cell lung cancer (NSCLC) with a frequency of approximately less than 1%. Next-generation sequencing (NGS) is of priority for detecting NTRK fusions, especially RNA-based NGS. Currently, the tropomyosin receptor kinase (TRK) inhibitors have shown promising efficacy and well tolerance in patients with NTRK fusion-positive solid tumors, regardless of tumor histology. The first-generation TRK inhibitors (larotrectinib and entrectinib) are reco

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties

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… Some of the most common genetic changes involved in this pathology are the mutation in or silencing of the genes involved in DNA mismatch repairs (MMR) mechanisms, such as MutS homolog 2 (MSH2) and the mutation of the adenomatous polyposis coli (APC) tumor suppressor gene, which regulates the Wnt/ β …

Research Progress of Immunotherapy for Gastric Cancer.

Gastric cancer (GC) is one of the most common gastrointestinal tract cancers worldwide, which has high incidence and mortality rates and poor prognosis. Although multidisciplinary comprehensive therapies consisting of surgery, chemotherapy, radiotherapy, and targeted therapy have made great progress in GC treatment, a satisfactory curative effect still cannot be achieved in many circumstances, and the 5-year survival of patients with GC remains to be very low. In China, about 75% of patients with GC are diagnosed in the advanced stage and thus miss the opportunity of surgical resection. Althou

Immunodiagnosis - the promise of personalized immunotherapy.

Immunotherapy showed remarkable efficacy in several cancer types. However, the majority of patients do not benefit from immunotherapy. Evaluating tumor heterogeneity and immune status before treatment is key to identifying patients that are more likely to respond to immunotherapy. Demographic characteristics (such as sex, age, and race), immune status, and specific biomarkers all contribute to response to immunotherapy. A comprehensive immunodiagnostic model integrating all these three dimensions by artificial intelligence would provide valuable information for predicting treatment response. H

Cancer Immunotherapy with Immune Checkpoint Inhibitors-Biomarkers of Response and Toxicity; Current Limitations and Future Promise.

Immune checkpoint inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and tumour mutational burden, none of which are particularly sensitive or specific. Emerging tumour

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… Microsatellite Instability Microsatellites are short sequences of base pair repeats which may become elongated or duplicated during DNA replication in the absence of the DNA mismatch repair (MMR) complex which repairs these errors. …

From the ASCO20 Virtual meeting.

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… In KEYNOTE-177, frontline pembrolizumab substantially improved disease control in patients with microsatellite instability-high and/or DNA mismatch repair-deficient metastatic colorectal cancer (median PFS 16.5 months versus 8.2 months with standard chemotherapy regimens; 24-month PFS 48.3% versus 18.6% …