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Polyphenols as Antitumor Agents Targeting Key Players in Cancer-Driving Signaling Pathways.

Polyphenols constitute an important group of natural products that are traditionally associated with a wide range of bioactivities. These are usually found in low concentrations in natural products and are now available in nutraceuticals or dietary supplements. A group of polyphenols that include apigenin, quercetin, curcumin, resveratrol, EGCG, and kaempferol have been shown to regulate signaling pathways that are central for cancer development, progression, and metastasis. Here, we describe novel mechanistic insights on the effect of this group of polyphenols on key elements of the signaling

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

Терапевтические и диагностические проблемы передневременного слабоумия.

В поисках терапевтических модификаторов фронтовременное слабоумие (ФТР) традиционно омрачалось другими заболеваниями, такими, как болезнь Альцгеймера (AD). Будучи клиническим и патологическим по своему характеру заболеванием, ПТО было вызвано рядом недавних открытий, таких, как новые генетические варианты семейных и спорадических форм заболеваний и выявление белка, связывающего ДНК с ДНК. 43 kDa (kDa)TDP-43) в качестве определяющего компонента включения более чем в половине случаев. В сочетании с постоянно расширяющимися знаниями о функции и дисфункции белка тау-а, который патологически агреги

Artificial intelligence in immunotherapy: revolutionizing diagnostic and therapeutic applications in cancer and autoimmune diseases.

Artificial intelligence (AI) is increasingly advancing precision immunotherapy by integrating high-dimensional biomedical data to support diagnosis, treatment selection, and longitudinal monitoring in both cancer and autoimmune diseases. This review summarizes AI applications in biomarker discovery, prediction of immune checkpoint inhibitor (ICI) response and toxicity, neoantigen prioritization, CAR-T cell optimization, and therapeutic antibody engineering. In oncology, multimodal models combining multi-omics, medical imaging, and clinical variables improve patient stratification and non-invas

Optimal Treatment of Retinal Vein Occlusion: An Updated Canadian Review and Recommendations.

Retinal vein occlusion (RVO) represents a heterogeneous group of disorders that remains the second most common retinal vascular disease and can be associated with vision loss. RVO confers a substantial burden of illness that affects patients, caregivers, medical systems, and physicians. Complications of RVO - including cystoid macular edema, macular ischemia, and neovascularization sequelae - may result in severe visual morbidity and blindness. Canadian expert consensus recommendations on the optimal treatment of patients with RVO were published in 2015. Since that time, advances in diagnosis

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… Francis JH , Diamond EL , Chi P , Jaben K , Hyman DM , Abramson DH . MEK inhibitor-associated central retinal vein occlusion associated with hyperhomocysteinemia and MTHFR variants . Ocul Oncol Pathol . 2020 ; 6 ( 3 ): 159 – 163 . doi: 10.1159/000501155 32509759 PMC7250324 79. …

Theranostics - a sure cure for cancer after 100 years?

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted d

Osteoid cell-derived chemokines drive bone-metastatic prostate cancer.

One of the greatest challenges in improving prostate cancer (PCa) survival is in designing new therapies to effectively target bone metastases. PCa regulation of the bone environment has been well characterized; however, bone-targeted therapies have little impact on patient survival, demonstrating a need for understanding the complexities of the tumor-bone environment. Many factors contribute to creating a favorable microenvironment for prostate tumors in bone, including cell signaling proteins produced by osteoid cells. Specifically, there has been extensive evidence from both past and recent

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… Lehrer S, Diamond EJ, Mamkine B, Stone NN, Stock RG. Serum interleukin-8 is elevated in men with prostate cancer and bone metastases. Technol Cancer Res Treat (2004) 3:411. doi: 10.1177/153303460400300501 45. Chi N, Tan Z, Ma K, Bao L, Yun Z. …

Bone-modifying therapy in multiple myeloma: a comprehensive review.

Multiple myeloma (MM) is a clonal hematologic malignancy characterized by plasma cell proliferation in the bone marrow. One of the most common clinical presentations is skeletal-related events (SREs), characterized by osteolysis of the bone, leading to a significant morbidity and mortality. The main aim of this review article is to provide an overview of the pathogenesis and evidence-based, guideline-recommended treatment of SREs. MM bone homeostasis is altered by numerous pathways and cytokines, leading to the pathogenesis of bone and osteolytic lesions. Historically, bisphosphonates were the

Модуляторные эффекты традиционной китайской медицины и производные активных метаболитов на аутоиммунально-воспалительных путях сигнала при множестве склерозов: обзор повествования.

Множественный склероз (MS) — нервно-воспалительное заболевание с иммунной помощью, характеризующееся обезвоживанием, аксоновой травмой и обширным разрушением целостности центральной нервной системы. Экспериментальный аутоиммунный энцефаломиэлит (EAE) — наиболее часто применяемая модель для имитации патологических особенностей человека. В настоящее время еще многое предстоит сделать для совершенствования стратегии лечения MS. Все больше исследований показывают, что традиционная китайская медицина (TCM) и связанные с ней активные метаболиты полезны для лечения MS и умело регулируют уровни подстр

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects.

Reconstruction of critical-sized bone defects remains a tremendous challenge for surgeons worldwide. Despite the variety of surgical techniques, current clinical strategies for bone defect repair demonstrate significant limitations and drawbacks, including donor-site morbidity, poor anatomical match, insufficient bone volume, bone graft resorption, and rejection. Bone tissue engineering (BTE) has emerged as a novel approach to guided bone tissue regeneration. BTE focuses on in vitro manipulations with seed cells, growth factors and bioactive scaffolds using bioreactors. The successful clinical

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… Mechanical properties of diamond lattice Ti–6Al–4V structures produced by laser powder bed fusion: On the effect of the load direction. J. Mech. Behav. Biomed. Mater. 2020;104:103656. doi: 10.1016/j.jmbbm.2020.103656. 122. Rabbani M., Zakian N., Alimoradi N. …

The role of polyamine metabolism in remodeling immune responses and blocking therapy within the tumor immune microenvironment.

The study of metabolism provides important information for understanding the biological basis of cancer cells and the defects of cancer treatment. Disorders of polyamine metabolism is a common metabolic change in cancer. With the deepening of understanding of polyamine metabolism, including molecular functions and changes in cancer, polyamine metabolism as a new anti-cancer strategy has become the focus of attention. There are many kinds of polyamine biosynthesis inhibitors and transport inhibitors, but not many drugs have been put into clinical application. Recent evidence shows that polyamin

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… Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med (2011) 208:1989–2003. doi: 10.1084/jem.20101158 151. …

Clinical and Therapeutic Implications of Epstein-Barr Virus in HIV-Related Lymphomas.

The incidence of lymphomas is increased in people living with HIV (PLWH). Aggressive B-cell non-Hodgkin lymphomas (NHLs) are the most common and are considered an AIDS-defining cancer (ADC). Although Hodgkin lymphoma (HL) is not considered an ADC, its incidence is also increased in PLWH. Among all HIV-related lymphomas (HRL), the prevalence of Epstein-Barr virus (EBV) is high. It has been shown that EBV is involved in different lymphomagenic mechanisms mediated by some of its proteins, contributing to the development of different lymphoma subtypes. Additionally, cooperation between both HIV an

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… Diamond C., Taylor T.H., Aboumrad T., Anton-Culver H. Changes in Acquired Immunodeficiency Syndrome-Related Non-Hodgkin Lymphoma in the Era of Highly Active Antiretroviral Therapy. Cancer. 2006;106:128–135. doi: 10.1002/cncr.21562. 42. …

Antibody-Drug Conjugates for Cancer Therapy.

Antibody-drug conjugates (ADCs) are novel drugs that exploit the specificity of a monoclonal antibody (mAb) to reach target antigens expressed on cancer cells for the delivery of a potent cytotoxic payload. ADCs provide a unique opportunity to deliver drugs to tumor cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows and enhanced pharmacokinetic/pharmacodynamic properties. To date, nine ADCs have been approved by the FDA and more than 80 ADCs are under clinical development worldwide. In this paper, we provide an overview of the biology and chemistry of each co

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… Diamond J.R. O’Shaughnessy J. Moroose R.L. Santin A.D. Abramson V.G. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer N. Engl. J. Med. 2019 380 741 751 10.1056/NEJMoa1814213 30786188 98. Trudel S. Lendvai N. Popat R. Voorhees P.M. Reeves B. Libby E.N. …

Does the Immunocompetent Status of Cancer Patients Have an Impact on Therapeutic DC Vaccination Strategies?

Although different types of therapeutic vaccines against established cancerous lesions in various indications have been developed since the 1990s, their clinical benefit is still very limited. This observed lack of effectiveness in cancer eradication may be partially due to the often deficient immunocompetent status of cancer patients, which may facilitate tumor development by different mechanisms, including immune evasion. The most frequently used cellular vehicle in clinical trials are dendritic cells (DCs), thanks to their crucial role in initiating and directing immune responses. Viable va

Antibodies to watch in 2018.

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody

Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile,

B-cell targeted therapeutics in clinical development.

B lymphocytes are the source of humoral immunity and are thus a critical component of the adaptive immune system. However, B cells can also be pathogenic and the origin of disease. Deregulated B-cell function has been implicated in several autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. B cells contribute to pathological immune responses through the secretion of cytokines, costimulation of T cells, antigen presentation, and the production of autoantibodies. DNA-and RNA-containing immune complexes can also induce the production of type

Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.

Cytokines are essential components of the tumor microenvironment (TME) and play crucial roles in tumor initiation and progression. As key mediators of interactions between immune cells and tumor cells within the TME, many cytokines exhibit both protumor and antitumor properties. This complex duality, reminiscent of the balance philosophy pursued by "Onmyoji" in traditional Eastern philosophy, which involves observing and regulating opposing forces to achieve harmony, poses marked challenges in translating cytokine therapies from animal studies to clinical applications. More than 20 key cytokin

Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).

Cancer therapy has undergone a remarkable evolution over the past few decades, driven largely by innovations in medicinal chemistry. This review explores the pivotal role of medicinal chemistry in designing, optimizing, and classifying anticancer agents, from traditional cytotoxics to modern targeted therapies, immunotherapies, and radiotheranostics. The article categorizes FDA-approved anticancer drugs (2015-2025), evaluates their mechanisms of action, structural features, and structure-activity relationships (SAR), and highlights both success stories and challenges in clinical translation. A

Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.

Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in pro