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From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor prognosis despite advances in treatment strategies. Standard treatment regimens induce remissions in many patients, but relapse occurs in approximately half, highlighting the urgent need for novel therapeutic strategies. Antibody-based therapies have significantly improved the treatment of acute lymphoblastic leukemia (ALL), but progress in AML has been slower, with only gemtuzumab ozogamicin (GO) receiving FDA approval to date. This is largely due to the absence of AML-specific surface antigens and the challeng

Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predic

Linking Iron Metabolism, Ferroptosis, and Cancer: New Targets and Prospects for Effective Anticancer Therapeutic Interventions.

New anticancer therapeutic strategies, including targeting of iron dysregulation in affected cancer types and stages, are urgently needed to decrease the associated annual cancer death rate of about 10 million worldwide. Many tumours evade treatment and support metastatic potential by effluxing iron and upregulating antioxidant systems, leading to suppression of lipid peroxidation and ferroptotic cell death. Similarly, many tumours manipulate the tumour microenvironment (TME) by ensuring the continuous supply of iron. This involves phenotypic modulation of immune cells, including macrophages,

CD11c + микроглиа: от базовых исследований к клиническому применению.

CD11c + микроглиа - функционально специализированная подгруппа микроглий, играющая ключевую роль в патофизиологических процессах различных заболеваний центральной нервной системы. Этот обзор обобщает убедительные доказательства того, что CD11c + микроглиа демонстрируют уникальные транскриптомные и фигоцитические характеристики. Эти характеристики отличают их от гомеостатической микроглии и поддерживают их специализированные функции. Во время разработки CD11c + микроглиа имеют решающее значение для созревания олигодендроцитов и целостности белой материи, особенно в таких регионах, как corpus ca

The γ-secretase complex: from discovery to a therapeutic target.

γ-Secretase is an intricate intramembrane aspartyl protease that cleaves within the transmembrane domain of ∼150 substrates and is considered the 'proteasome of the membrane'. This enzyme consists of four different subunits, with presenilin being the catalytic subunit. This review provides a brief overview of γ-secretase as a proteolytic enzyme, from its biochemistry and biology to its roles in disease and potential as a therapeutic target. A detailed discussion on the discovery and structure of γ-secretase is followed by a survey of its substrates, including the most studied amyloid precursor

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… Qi-Takahara Y. Morishima-Kawashima M. Tanimura Y. Dolios G. Hirotani N. Horikoshi Y. Kametani F. Maeda M. Saido T. C. Wang R. Ihara Y. Longer Forms of Amyloid β Protein: Implications for the Mechanism of Intramembrane Cleavage by γ-Secretase. J. … Qi Y. Kakuda N. Misonou H. Mitsumori R. Maruyama H. Koo E. H. Haass C. Takio K. Morishima-Kawashima M. Ishiura S. Ihara Y. Potential Link between Amyloid β-Protein 42 and C-terminal Fragment γ 49–99 of β-Amyloid Precursor Protein. J. Biol. …

Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.

The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA changes, often precede genetic mutations and are critical in cancer progression. In this study, we explore how liquid biopsy, combined with epigenetic markers, can provide early detection of lung cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges of targeting epigenetic regulators, which could disrupt cellul

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… J Clin Oncol . 2009 ; 27 ( 34 ): 5823 ‐ 5829 . 19826114 10.1200/JCO.2009.23.1738 90 Chen Z , Fan Y , Liu X , Shang X , Qi K , Zhang S . Clinicopathological significance of DAPK gene promoter hypermethylation in non‐small cell lung cancer: A meta‐analysis . …

Current Landscape and Future Directions in Cancer Immunotherapy: Therapies, Trials, and Challenges.

Cancer remains a leading global health challenge, placing immense burdens on individuals and healthcare systems. Despite advancements in traditional treatments, significant limitations persist, including treatment resistance, severe side effects, and disease recurrence. Immunotherapy has emerged as a promising alternative, leveraging the immune system to target and eliminate tumour cells. However, challenges such as immunotherapy resistance, patient response variability, and the need for improved biomarkers limit its widespread success. This review provides a comprehensive analysis of the curr

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… Qi S. Chen X. Zhang H. Ni Z. Zhou Y. Chen G. The roles and mechanism of m(6)A RNA methylation regulators in cancer immunity Biomed. Pharmacother. = Biomed. Pharmacother. 2023 163 114839 10.1016/j.biopha.2023.114839 37156113 10. Zeng Q. Jiang T. Wang J. Role of LMO7 in cancer (Review) Oncol. … Qi R. Liu W. Li M. Guo M. Wei L. Yao Z. Indoleamine 2,3-Dioxygenase 1: A Promising Therapeutic Target in Malignant Tumor Front Immunol 2021 12 800630 10.3389/fimmu.2021.800630 35003126 PMC8733291 57. Fujiwara Y. Kato S. Nesline M.K. Conroy J.M. DePietro P. Pabla S. Kurzrock R. …

Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.

Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that f

A Comprehensive Review of Immunotherapy Clinical Trials for Metastatic Urothelial Carcinoma: Immune Checkpoint Inhibitors Alone or in Combination, Novel Antibodies, Cellular Therapies, and Vaccines.

Urothelial cancer is an immune-responsive cancer, but only a subset of patients benefits from immune checkpoint inhibition. Currently, single-agent immune checkpoint inhibitors (ICIs) and the combination of pembrolizumab with the antibody-drug conjugate enfortumab vedotin are approved to treat patients with metastatic UC (mUC). Approval of first-line nivolumab in combination with gemcitabine and cisplatin is expected imminently. Many treatment approaches are being investigated to better harness the immune system to fight mUC. In this review, we summarize the landmark clinical trials of ICIs th

Nanoparticles and bone microenvironment: a comprehensive review for malignant bone tumor diagnosis and treatment.

Malignant bone tumors, which are difficult to treat with current clinical strategies, originate from bone tissues and can be classified into primary and secondary types. Due to the specificity of the bone microenvironment, the results of traditional means of treating bone tumors are often unsatisfactory, so there is an urgent need to develop new treatments for malignant bone tumors. Recently, nanoparticle-based approaches have shown great potential in diagnosis and treatment. Nanoparticles (NPs) have gained significant attention due to their versatility, making them highly suitable for applica

Microbiome and pancreatic cancer: time to think about chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by late diagnosis, rapid progression, and a high mortality rate. Its complex biology, characterized by a dense, stromal tumor environment with an immunosuppressive milieu, contributes to resistance against standard treatments like chemotherapy and radiation. This comprehensive review explores the dynamic role of the microbiome in modulating chemotherapy efficacy and outcomes in PDAC. It delves into the microbiome's impact on drug metabolism and resistance, and the interaction between microbial elements, drugs,

Connection between nutrition and oncology in dogs and cats: perspectives, evidence, and implications-a comprehensive review.

Oncology has become one of the most influential and studied areas in both human and companion animal health. In veterinary practice, cancer represents a significant challenge, especially concerning cats and dogs. Nutrition plays a crucial role in the management of oncology patients in veterinary medicine; however, is often nonspecific and reliant on data from other species and diseases, highlighting the need for a comprehensive review of the latest developments in this field. Since the intricate relationship between nutrition and cancer encompasses various aspects, this review therefore intend

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… He C Chen X Chen Y Sun J Qi M Rocha S . Global acetylome profiling indicates EPA impedes but OA promotes prostate cancer motility through altered acetylation of PFN1 and FLNA . Proteomics . ( 2024 ) 24 : e2300393 – 12 . doi: 10.1002/pmic.202300393 , PMID: 38430206 19. Ness RA Miller DD Li W . …

Trials and Tribulations of MicroRNA Therapeutics.

The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Cons

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… Qi X. Wang Y. Ren J. Regulatory network of miRNA on its target: Coordination between transcriptional and post-transcriptional regulation of gene expression Cell. Mol. Life Sci. 2019 76 441 451 10.1007/s00018-018-2940-7 30374521 PMC11105547 92. van Rooij E. The art of microRNA research Circ. …

Exploring the dual role of B cells in solid tumors: implications for head and neck squamous cell carcinoma.

In the tumor milieu of head and neck squamous cell carcinoma (HNSCC), distinct B cell subpopulations are present, which exert either pro- or anti-tumor activities. Multiple factors, including hypoxia, cytokines, interactions with tumor cells, and other immune infiltrating lymphocytes (TILs), alter the equilibrium between the dual roles of B cells leading to cancerogenesis. Certain B cell subsets in the tumor microenvironment (TME) exhibit immunosuppressive function. These cells are known as regulatory B (Breg) cells. Breg cells suppress immune responses by secreting a series of immunosuppressi

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… Hu Q, Hong Y, Qi P, Lu G, Mai X, Xu S, et al. Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling. Nat Commun (2021) 12:2186. doi: 10.1038/s41467-021-22300-2 30. … Cillo AR, Kürten CHL, Tabib T, Qi Z, Onkar S, Wang T, et al. Immune landscape of viral- and carcinogen-driven head and neck cancer. Immunity (2020) 52:183–199.e9. doi: 10.1016/j.immuni.2019.11.014 105. Koneva LA, Zhang Y, Virani S, Hall PB, McHugh JB, Chepeha DB, et al. …

CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges.

Chimeric antigen receptor T (CAR-T) cell therapy represents a major breakthrough in cancer treatment, and it has achieved unprecedented success in hematological malignancies, especially in relapsed/refractory (R/R) B cell malignancies. At present, CD19 and BCMA are the most common targets in CAR-T cell therapy, and numerous novel therapeutic targets are being explored. However, the adverse events related to CAR-T cell therapy might be serious or even life-threatening, such as cytokine release syndrome (CRS), CAR-T-cell-related encephalopathy syndrome (CRES), infections, cytopenia, and CRS-rela

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… Exp Hematol ( 2002 ) 30 ( 11 ): 1283–92 . doi: 10.1016/s0301-472x(02)00921-9 12423681 106 Qi C Tian S Wang J Ma H Qian K Zhang X . Co-Expression of CD40/CD40L on XG1 Multiple Myeloma Cells Promotes IL-6 Autocrine Function . … Front Oncol ( 2021 ) 11 : 798352 . doi: 10.3389/fonc.2021.798352 35004324 PMC8733571 156 Wang Y Qi K Cheng H Cao J Shi M Qiao J . Coagulation Disorders After Chimeric Antigen Receptor T Cell Therapy: Analysis of 100 Patients With Relapsed and Refractory Hematologic Malignancies . …

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Androgen deprivation therapy (ADT) for metastatic and high-risk prostate cancer (PC) inhibits growth pathways driven by the androgen receptor (AR). Over time, ADT leads to the emergence of lethal castrate-resistant PC (CRPC), which is consistently caused by an acquired ability of tumors to re-activate AR. This has led to the development of second-generation anti-androgens that more effectively antagonize AR, such as enzalutamide (ENZ). However, the resistance of CRPC to ENZ develops rapidly. Studies utilizing preclinical models of PC have established that inhibition of the Jak2-Stat5 signaling

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… Qi et al. demonstrated that AT9283 induced apoptosis and inhibited cell proliferation in B-Non-Hodgkin lymphoma (B-NHL) cell lines at an IC50 < 1 μM in a dose- and time-dependent manner. …

Inflammation in cancer: therapeutic opportunities from new insights.

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors

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… AKT and ERK signaling | Wang X et al., 2019 Pancreatic cancer | Promote | Promotes proliferation, invasion and migration by stimulating AKT signal transduction | Wang X et al., 2020 IL-24 | IL-20Rα,IL-20Rβ, IL-22Rα1, IL-20Rβ | Lung cancer | Inhibit | Inhibits proliferation and promotes apoptosis | Qi …

Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health burden, including both acute infections and persistent post-acute sequelae, also known as Long COVID (LC) in survivors. While clinical management has reduced case-fatality rates, a substantial proportion of patients develop LC, a heterogeneous syndrome with long-term symptoms. This complex continuum requires therapeutic strategies for both the acute and chronic phases. Plasma proteomics has emerged as a powerful tool in precision medicin

CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.

CRISPR-Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targ

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… Qi W. Hruzova M. Kissling L. Lenggenhager D. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels Nat. Biotechnol. 2021 39 949 957 10.1038/s41587-021-00933-4 34012094 PMC8352781 75. Lee R.G. Mazzola A.M. Braun M.C. Platt C. Vafai S.B. Kathiresan S. Rohde E. …

The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) T cells have demonstrated remarkable ability to render multiple relapsed and refractory patients into a deep and often durable remission. Since initial FDA approval of tisagenlecleucel in 2017, real-world data have shown the benefit of this therapy, even among historically complex populations, such as infants, children with Down syndrome, and those with extramedullary leukemia. Despite the success of CAR T cell therapy, nearly half of patients tend to show relapsed disease, demanding ongoing advancements. Furthermore, the incorporation of the bispecific T cell e

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… Qi Y., Zhao M., Hu Y., Wang Y., Li P., Cao J., Shi M., Tan J., Zhang M., Xiao X., et al. Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL. Blood. 2022;139:3376–3386. doi: 10.1182/blood.2021013733. 44. …