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Engineering precision nanoparticles for drug delivery.

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value.

Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In t

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… Nivolumab Versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer . N Engl J Med ( 2015 ) 373 ( 17 ): 1627–39 . doi: 10.1056/NEJMoa1507643 PMC5705936 26412456 18 Wang H Agulnik J Kasymjanova G Fiset PO Camilleri-Broet S Redpath M . …

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets.

Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient's own immune system to selectively kill cancer cells. The immune system is the body's main cancer surveillance system, but cancers may evade destruction thanks to various immune-suppressing mechanisms. We therefore need to deploy various immunotherapy-based strategies to help bolster the anti-tumour immune responses. These include engineering T cells to express chimeric antigen receptors (CARs) to specifically recogni

Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL).

A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTO

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… Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2015;373(17):1627–1639. doi: 10.1056/NEJMoa1507643. 44. …

Passive Monoclonal and Polyclonal Antibody Therapies

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… In phase III clinical trials, nivolumab performed better than docetaxel in the treatment of NSCLC. 243 , 244 , 245 Ovarian/cervical fallopian cancer Bevacizumab (Avastin) is FDA approved for treatment of locally advanced, recurrent or metastatic, ovarian, cervical, and fallopian cancers after treatment …

Role of mitochondria in physiological activities, diseases, and therapy.

Mitochondria are generally considered essential for life in eukaryotic organisms because they produce most of the energy or adenosine triphosphate (ATP) needed by the cell. Beyond energy production, it is now widely accepted that mitochondria also play a pivotal role in maintaining cellular homeostasis and signaling. The two core processes of mitochondrial dynamics, fission and fusion, serve as crucial foundations for maintaining mitochondrial morphology, distribution, and quantity, thereby ensuring cellular homeostasis. Mitochondrial autophagy (mitophagy) ensures the selective degradation of

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… supplement NCT00950248 Coconut oil + Epigallocatechin gallate Phase II Antioxidant NCT03740295 D-aspartate + IFN β−1a + Methylprednisolone Phase II Combination therapy NCT03387046 Juvenile idiopathic arthritis CoQ10 Phase II/III Antioxidant NCT05871086 Solid tumors BGB-24714 ± Paclitaxel ± Carboplatin ± Docetaxel … oil + Epigallocatechin gallate | Phase II | Antioxidant | NCT03740295 | D-aspartate + IFN β−1a + Methylprednisolone | Phase II | Combination therapy | NCT03387046 Juvenile idiopathic arthritis | CoQ10 | Phase II/III | Antioxidant | NCT05871086 Solid tumors | BGB-24714 ± Paclitaxel ± Carboplatin ± Docetaxel …

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

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… 4.8 months in the treatment group, and the placebo arm was just 0.9 months. 167 The indolinone derivative nintedanib targets VEGFR-1/2/3, FGFR1/2, and PDGFRα/β. 168 It was initially used clinically for the treatment of idiopathic pulmonary fibrosis 169 and the combination therapy of nintedanib and docetaxel …

Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.

The ability of small nucleic acids to modulate gene expression via a range of processes has been widely explored. Compared with conventional treatments, small nucleic acid therapeutics have the potential to achieve long-lasting or even curative effects via gene editing. As a result of recent technological advances, efficient small nucleic acid delivery for therapeutic and biomedical applications has been achieved, accelerating their clinical translation. Here, we review the increasing number of small nucleic acid therapeutic classes and the most common chemical modifications and delivery platf

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… utilized for gene delivery. 334 The 6th generation of dendritic poly(L-lysine) (KG6), with 128 amine groups on its surface, was demonstrated to be an efficient siRNA carrier with minimal cytotoxicity. 335 Another star-shaped copolymer consisting of a β-cyclodextrin core and PLL dendron arms was used for docetaxel …

The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic framework

Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.

Cancer is more than just a collection of tumor cells. The complex tumor system, including the tumor immune microenvironment (TIME), is continually changing. Tumor cells are in constant communication with all stromal elements (e.g., fibroblasts, endothelial cells, and extracellular matrix) and immune effector cells (e.g., T cells, B cells, natural killer cells, dendritic cells, macrophages, and myeloid-derived suppressor cells). Together, these intricate interactions among cell and molecular signaling pathways collectively drive tumor growth, tumor invasion, and metastasis and significantly aff

Immunologic tumor microenvironment modulators for turning cold tumors hot.

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein

Involvement of the Opioid Peptide Family in Cancer Progression.

Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins

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… Methylnaltrexone (mu-opioid receptor antagonist) increased the activity of the antitumor drug docetaxel by inhibiting gastric cancer cell growth-suppressive pathways in vivo [ 293 ]. …

Role of PARP Inhibitors in Cancer Immunotherapy: Potential Friends to Immune Activating Molecules and Foes to Immune Checkpoints.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxic effects as single agents in tumors characterized by defective repair of DNA double-strand breaks deriving from BRCA1/2 mutations or other abnormalities in genes associated with homologous recombination. Preclinical studies have shown that PARPi-induced DNA damage may affect the tumor immune microenvironment and immune-mediated anti-tumor response through several mechanisms. In particular, increased DNA damage has been shown to induce the activation of type I interferon pathway and up-regulation of PD-L1 expression in cance

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… The KEYLYNK-010 ( NCT03834519 ) is a phase 3 trial currently assessing the efficacy and safety of olaparib plus pembrolizumab in mCRPC patients pre-treated with enzalutamide or abiraterone that had progressed following docetaxel treatment [ 308 ]. …

Apoptotic Pathway as the Therapeutic Target for Anticancer Traditional Chinese Medicines.

Cancer is a leading cause of morbidity and mortality worldwide. Apoptosis is a process of programmed cell death and it plays a vital role in human development and tissue homeostasis. Mounting evidence indicates that apoptosis is closely related to the survival of cancer and it has emerged as a key target for the discovery and development of novel anticancer drugs. Various studies indicate that targeting the apoptotic signaling pathway by anticancer drugs is an important mechanism in cancer therapy. Therefore, numerous novel anticancer agents have been discovered and developed from traditional

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… Clinical study of 76 patients with gastric cancer showed that the anticancer efficacy was markedly increased and drug-induced toxicity was significantly decreased when cinobufacin was combined with different chemotherapeutic drugs such as docetaxel, cisplatin, or 5-fluorouracil and therefore improved …

Targeting the proteasome in cancer therapy: development and future opportunities in natural products.

BACKGROUND: The ubiquitin-proteasome pathway is a critical therapeutic target in malignancies, particularly multiple myeloma. The development of proteasome inhibitors (PIs) has marked a milestone in multiple myeloma therapy and now constitutes the backbone of frontline treatment regimens. However, primary and acquired resistance remain a major challenge, underscoring the need to identify new PIs as well as agents that can resensitize resistant cells. METHOD: This review provides an overview of the current clinical applications of PIs and offers a comprehensive summary of natural products that

Митохондриальная передача метаболических перепрограмм и лекарственная устойчивость в метастазе костей: механизмы и терапевтические стратегии.

Кость это one из наиболее распространенных участков удаленного метастаза в твердых опухолях, в частности рак груди, рак простаты и рак легких. Метатические повреждения костей часто свидетельствуют о стойком сопротивлении многосистемной терапии, включая химиотерапию, целевую терапию, эндокринную терапию и ингибиторы иммунных контрольно-пропускных пунктов (ИПК). Накопляющиеся данные свидетельствуют о том, что метаболическая перепрограммирование в пределах костной микроокружающей среды способствует этому сопротивлению, однако механизмы в верхнем течении по-прежнему недостаточно понятны. В качеств

Advancing cancer therapy: Nanomaterial-based encapsulation strategies for enhanced delivery and efficacy of curcumin.

Curcumin, a polyphenolic compound derived from Curcuma longa, has gained significant attention as a potential anticancer agent due to its anti-inflammatory, antioxidant, and antitumor properties. Despite its therapeutic potential, the clinical application of curcumin is limited by its poor aqueous solubility, rapid metabolism, and limited bioavailability. To address these limitations, various nanomaterial-based encapsulation strategies have been developed, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, micelles, dendrimers, and hybrid nanomaterials. These formulations

Предварительная обработка сигнатуры эндокринного недоедания прогнозируют клиническую пользу от PD-1/PD-L1 Блокирование гематологовых магнатов.

Гематологические заболевания создают значительное бремя для здоровья людей во всем мире, а запрограммированная клеточная смертность protein-1 (В тыс.PD-1)/запрограммированный смертельный лиганж клеток 1 (В тыс.PD-L1) ингибиторы, революционизирующие лечение в подтипах, таких, как классическая лимфома Ходжкина (cHL) и первичная медистинальная лимфома В-клеток (PMBCL), достигающая высоких объективных показателей ответов (ORR). Однако эффективность варьируется в широких пределах, при этом успех в множестве миеломы ограничен.< 10% ORR) и лейкемии, подчеркивая необходимость лучшего прогнозирования,

Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?

Despite significant progress in cancer prevention, screening, and treatment, the still limited number of therapeutic options is an obstacle towards increasing the cancer cure rate. In recent years, many efforts were put forth to develop therapeutics that selectively target different components of the oncogenic Wnt/β-catenin signaling pathway. These include small molecule inhibitors, antibodies, and more recently, gene-based approaches. Although some of them showed promising outcomes in clinical trials, the Wnt/β-catenin pathway is still not targeted in routine clinical practice for cancer mana

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment.

Cancer progression and metastasis due to tumor immune evasion and drug resistance is strongly associated with immune suppressive cellular responses, particularly in the case of metastatic tumors. The myeloid cell component plays a key role within the tumor microenvironment (TME) and disrupts both adaptive and innate immune cell responses leading to loss of tumor control. Therefore, strategies to eliminate or modulate the myeloid cell compartment of the TME are increasingly attractive to non-specifically increase anti-tumoral immunity and enhance existing immunotherapies. This review covers cur

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… Carlumab has demonstrated positive clinical responses when used in combination with chemotherapeutic drug docetaxel ( 123 ); phase II trials have been completed but Carlumab has since been discontinued ( NCT00992186 ). …