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Drug-induced oxidative stress in cancer treatments: Angel or devil?

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox

Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.

Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, i

NK cell based immunotherapy against oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck cancers, presents significant challenges due to its aggressive feature and limited therapeutic efficacy of conventional treatments. In response to these challenges, Natural Killer (NK) cells, a vital component of the innate immune system, are being explored for their therapeutic potential in OSCC due to their inherent ability to target and eliminate cancer cells without prior sensitization. This review uniquely focuses on the evolving role of NK cells specifically in OSCC, incorporating recent advancements in CAR-NK cell eng

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… Knocking down HPSE expression reduced the proliferation rate of SCC-25 cells, leading to a significant increase in the percentage of cells in the G0/G1 phase, and suppressed cell migration and invasion. E-cadherin mRNA and protein expression increased, while Snail and Vimentin expression decreased. …

One step further in targeting acute leukemia by combining antibody-based immunotherapies and small molecule inhibitors.

BackgroundAcute leukemia is a bone marrow-related disease characterized by fast progression and the production of immature blood cells rather than normal ones that are classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Chemotherapy as a conventional treatment has many side effects, thus new medications that target intracellular molecules and cell surface markers on leukemic cells have been developed in the last decades.Main bodyThis review focuses on antibody-based targeted treatments, which so far, have been shown to improve the treatment outcomes, includ

The Development of Novel Therapies for Chronic Lymphocytic Leukaemia in the Era of Targeted Drugs.

Over the past decade, chronic lymphocytic leukaemia (CLL) treatment has shifted from chemoimmunotherapy to targeted oral agents, predominantly Bruton's tyrosine kinase inhibitors (BTKis) and the BCL-2 inhibitor venetoclax. These therapies have significantly improved outcomes and are now established as first-line treatment options. However, CLL remains incurable, and resistance or intolerance to both drug classes (double-refractory disease) is an emerging challenge. This has driven the development of novel therapeutic strategies, including non-covalent BTKis such as pirtobrutinib and nemtabruti

Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.

Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation

Systemic lupus erythematosus: pathogenesis and targeted therapy.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress

Bispecific antibodies in the treatment of multiple myeloma.

The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various

Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth.

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following forma

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… DTC exist in a quiescent state within the hematopoietic stem cell niche, fluctuating between the G0 and G1 phase of the cell cycle [ 11 , 49 , 50 , 51 , 52 ]. In this state of solitary cell dormancy, the DTC are resistant to chemotherapy and can avoid immune detection [ 53 , 54 , 55 , 56 ]. …

Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Rec

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lympho

Epigenetic drugs in cancer therapy: mechanisms, immune modulation, and therapeutic applications.

Epigenetic regulation is a fundamental mechanism controlling gene expression and cellular function, primarily mediated through reversible modifications such as DNA methylation, histone acetylation, and chromatin remodeling. Dysregulation of critical epigenetic enzymes, including histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and bromodomain and extraterminal domain (BET) proteins, has been closely associated with tumor initiation, progression, metastasis, immune evasion, and resistance to conventional therapies. Targeting these epigenetic regulators with small-molecule inhibitor

Is Systemic Immunosuppression a Risk Factor for Oral Cancer? A Systematic Review and Meta-Analysis.

Even if the relationship between immunosuppression and increased incidence of systemic cancers is well known, there is less awareness about the risk of developing oral cancer in immunosuppressed patients. The aim of this review was to evaluate the association between immunosuppression and the development of oral cancer. Two authors independently and, in duplicate, conducted a systematic literature review of international journals and electronic databases (MEDLINE via OVID, Scopus, and Web of Science) from their inception to 28 April 2023. The assessment of risk of bias and overall quality of e

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… Effect of 5-fluorouracil on G1 phase cell cycle regulation in oral cancer cell lines Oral Oncol. 2004 40 63 70 10.1016/S1368-8375(03)00136-2 14662417 211. Mawardi H. Elad S. Correa M.E. Stevenson K. Woo S.B. Almazrooa S. Haddad R. Antin H.J. Soiffer R. Treister H. …

Passive Monoclonal and Polyclonal Antibody Therapies

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Metabolic reprogramming in cancer and senescence.

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being the aging of the global population. Statistical data show that cancer incidence and mortality rates show a clear upward trend with age. Although there is a commonality between dysregulated nutrient sensing, which is one of the main features of aging, and metabolic reprogramming of tumor cells, the specific regulatory relationship is not clear. This manuscript intends to comprehensively analyze the relationship between senescence and tumor metabolic reprogramming; as well as reveal the impac

An Appraisal of the Oleocanthal-Rich Extra Virgin Olive Oil (EVOO) and Its Potential Anticancer and Neuroprotective Properties.

Dietary consumption of olive oil represents a key pillar of the Mediterranean diet, which has been shown to exert beneficial effects on human health, such as the prevention of chronic non-communicable diseases like cancers and neurodegenerative diseases, among others. These health benefits are partly mediated by the high-quality extra virgin olive oil (EVOO), which is produced mostly in Mediterranean countries and is directly made from olives, the fruit of the olive tree (Olea europaea L.). Preclinical evidence supports the existence of antioxidant and anti-inflammatory properties exerted by t

CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool.

Bacteriophages are pervasive viruses that infect bacteria, relying on their genetic machinery to replicate. In order to protect themselves from this kind of invader, bacteria developed an ingenious adaptive defence system, clustered regularly interspaced short palindromic repeats (CRISPR). Researchers soon realised that a specific type of CRISPR system, CRISPR-Cas9, could be modified into a simple and efficient genetic engineering technology, with several improvements over currently used systems. This discovery set in motion a revolution in genetics, with new and improved CRISPR systems being

Organic Nanoparticles in Progressing Cardiovascular Disease Treatment and Diagnosis.

Cardiovascular diseases (CVDs), the world's most prominent cause of mortality, continue to be challenging conditions for patients, physicians, and researchers alike. CVDs comprise a wide range of illnesses affecting the heart, blood vessels, and the blood that flows through and between them. Advances in nanomedicine, a discipline focused on improving patient outcomes through revolutionary treatments, imaging agents, and ex vivo diagnostics, have created enthusiasm for overcoming limitations in CVDs' therapeutic and diagnostic landscapes. Nanomedicine can be involved in clinical purposes for CV

Research progress on the clinical application and mechanism of iguratimod in the treatment of autoimmune diseases and rheumatic diseases.

Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modi

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… Gao Qiuying et al. confirmed in vitro that iguratimod can block the G0/G1 phase of MM cells by down-regulating CDK2 protein levels, thereby inhibiting the proliferation of myeloma cell line U226; it can also induce apoptosis of RPMI822 cells by up-regulating the expression of Bax protein that promotes …

Switching Homes: How Cancer Moves to Bone.

Bone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to "switch homes" and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the concept of "vicious cycle" and "osteolytic" vs. "osteosclerotic" bone metastases; as well as on novel co