Search Results (418)

Background: Thymic epithelial tumors (TETs), including thymic carcinomas and thymomas, are rare malignancies originating in the mediastinum. Therapeutic options remain limited for patients experiencing disease progression following platinum-based chemotherapy. High tumor mutational burden (TMB) is uncommon in thymic malignancies but may predict response to immunotherapy. We report a patient with TMB-high TET who participated in the KOSMOS-II study in South Korea and achieved a durable response to atezolizumab without developing immune-related adverse events (irAEs). Case presentation: A 73-year-old woman who had been treated for thymoma 20 years ago presented with a left neck mass. A biopsy of the neck mass confirmed recurrent thymoma, type B3, and her disease progressed despite platinum-based chemotherapy and subsequent pemetrexed treatment. TMB-high thymoma is very rare, but based on the next-generation sequencing (NGS) results, she was diagnosed with TMB-high (20.3 mutations/Mb) thymoma. As TMB-based immunotherapy is not approved in Korea, she was enrolled in the KOSMOS-II study and initiated on atezolizumab following molecular tumor board review. She achieved stable disease after three cycles and has remained progression-free for 14 months, completing 20 cycles without significant irAEs. Notably, her underlying myasthenia gravis did not worsen during treatment. Conclusions: This case demonstrates a favorable outcome with biomarker-directed ICI treatment in recurrent thymoma with limited treatment options, highlighting the importance of appropriate molecular markers to predict drug response. Although TMB-based immunotherapy is FDA-approved in the U.S., it remains unavailable in Korea, underscoring the need to explore flexible access pathways, including the potential use of immunotherapy beyond current indications, to improve treatment options for patients with life-threatening conditions. Full article

Skin cancer (SC) is the most prevalent malignancy worldwide, with subtypes varying in aggressiveness: basal cell carcinoma tends to be locally invasive, squamous cell carcinoma has a higher metastatic risk, and melanoma remains the deadliest form. Current treatments such as surgery, radiotherapy, and systemic chemotherapy are associated with aesthetic and functional morbidity, recurrence, and/or systemic toxicity. Although targeted therapies and immunotherapies offer clinical benefits, their high cost and limited accessibility underscore the need for innovative, affordable alternatives. Metal-based compounds (metallopharmaceuticals) are promising anticancer agents due to their ability to induce oxidative stress, modulate redox pathways, and interact with DNA. However, clinical translation has been limited by poor aqueous solubility, rapid degradation, and low skin permeability. This review discusses the most recent preclinical findings on gold, silver, platinum, palladium, ruthenium, vanadium, and copper complexes, mainly in topical and systemic treatments of SC. Advances in chemical and physical enhancers, such as hydrogels and microneedles, and in drug delivery systems, including bacterial nanocellulose membranes and nanoparticles, as well as liposomes and micelles, for enhancing skin permeation and protecting the integrity of metal complexes are also discussed. Additionally, we examine the contribution of photodynamic therapy to SC treatment and the use of mathematical and computational modeling to simulate skin drug transport, predict biodistribution, and support rational nanocarrier design. Altogether, these strategies aim to bridge the gap between physicochemical innovation and clinical applicability, paving the way for more selective, stable, and cost-effective SC treatments. Full article

According to the World Health Organization, breast cancer is the cancer that affects the largest number of people each year, especially women. Millions of women are diagnosed with it each year, and hundreds of thousands die from it. Research into new types of drugs, including metal complexes, including those containing tetradentate Schiff bases as ligands, offers a chance to reduce this number. Various cell lines are being used to test their effectiveness in cancer therapy, with the MCF-7 cancer cell line being the most commonly used. A literature search was conducted in four major databases: PubMed, SciELO. The Boolean operator “and” was used to refine the search strategy, combining the terms Schiff base, breast cancer, MCF-7 and metal complexes. Studies published between 2020 and 2025 investigating the cytotoxic activity of metal complexes with Schiff base ligands on the MCF-7 breast cancer cell line were included in the analysis. Articles were considered eligible if they were written in English. As a result of the database search, 37 scientific articles were selected and divided into three groups based on the ligand structure. The largest group of articles described the synthesis, structure, and anticancer activity of metal complexes with ligands based on the salicylaldehyde structure. These were included in the first group of complexes described. The second, extremely interesting and promising group of compounds consisted of metal complexes with ligands containing a sulfur atom. The last group included metal complexes with Schiff base ligands that were not included in the two previously mentioned groups. As indicated by the research results contained in the reviewed articles, Schiff base metal complexes constitute an interesting group of compounds characterized by a range of activities, including anticancer activity, which may in the future be used in anticancer therapy. They may also represent a cheaper and more effective alternative to platinum-based drugs. Full article

Cisplatin, a platinum-based compound, is a cornerstone of modern chemotherapy and remains widely used against a variety of solid tumors, including testicular, ovarian, lung, bladder, and head and neck cancers. Its anticancer activity is primarily attributed to the formation of DNA crosslinks, which obstruct replication and repair, ultimately leading to apoptosis. However, the clinical value of cisplatin is constrained by two major challenges: its toxic profile and the development of resistance. Cisplatin toxicity arises from its interaction not only with tumor DNA but also with proteins and nucleic acids in healthy tissues, resulting in a range of adverse effects, including, but not limited to, nephrotoxicity, ototoxicity, neurotoxicity, and gastrointestinal injury. In pediatric patients, permanent hearing loss represents a particularly debilitating complication. On the other hand, tumor cells can evade cisplatin cytotoxicity through diverse mechanisms, including reduced intracellular drug accumulation, enhanced DNA repair, detoxification by thiol-containing molecules, and alterations in apoptotic signaling. These resistance pathways severely compromise treatment outcomes and often necessitate alternative or combination strategies. This review examines the chemical structure of cisplatin, the molecular mechanisms of cisplatin cytotoxicity and cisplatin-induced resistance, as well as the main applications in cancer management and the complications associated with its clinical use. Full article

Carboxymethylcellulose (CMC) is a biocompatible and biodegradable polysaccharide suitable for biomedical applications. Herein, an epichlorohydrin (ECH)-crosslinked CMC hydrogel (CMCG) was developed as a carrier for sustained drug release. Ether-type crosslinking between the hydroxyl groups of CMC and ECH yielded a transparent, highly water-absorbent gel. Structural analyses employing Fourier-transform infrared and solid-state ¹³C nuclear magnetic resonance spectroscopies confirmed successful crosslinking, and the hydrogel exhibited pH-dependent swelling. Carboplatin (CBP), a platinum-based anticancer drug, was incorporated into CMCG to prepare CBP-CMCG. In phosphate-buffered saline (pH 7.4), approximately 70% of CBP was released within 12 h, followed by a plateau phase, indicating diffusion-controlled release. Cytocompatibility assays using WI-38 normal human fibroblasts demonstrated that CMCG was non-cytotoxic, whereas free CBP induced significant cell death. In colorectal cancer HT-29 cells, CBP-CMCG exhibited gradual cytotoxicity, resulting in >80% nonviable cells after 24 h, indicating a sustained antitumor effect compared with free CBP. These results demonstrate that the newly developed ECH-crosslinked CMC hydrogel is a safe and effective platform for controlled drug delivery, enabling sustained release and prolonged therapeutic activity of CBP. Full article

Platinum-based drugs play a pivotal role in contemporary cancer treatment, but their therapeutic utility is often limited by acquired resistance. The diiodido analog, cis-[PtI₂(NH₃)₂] is a promising derivative that has demonstrated the ability to overcome cisplatin resistance in vitro. To establish the molecular basis for this superior activity, we integrated experimental (NMR) spectroscopy with computational density functional theory (DFT) methods to precisely and comparatively understand the drug activation mechanisms. Comparative ¹⁴N NMR experiments elucidated the initial ligand substitution step, confirming halide displacement and a markedly higher tendency for ammonia release from cis-[PtI₂(NH₃)₂], particularly when reacting with sulfur-containing amino acids. Complementary DFT calculations determined the substitution energy values, revealing that the superior leaving-group ability of iodide results in a thermodynamically more favorable activation. Conceptual DFT parameters (softness, hardness, and Fukui indices) further demonstrated that initial substitution induces a strong trans effect, leading to the electronic sensitization of the remaining iodide ligand. This strong agreement between computational predictions and experimental data establishes a coherent molecular activation mechanism for cis-[PtI₂(NH₃)₂], demonstrating that iodide substitution promotes both thermodynamic and electronic activation of the platinum center, which is the key to its distinct pharmacological profile and ability to circumvent resistance. Full article

Background: Muscle-invasive bladder cancer (MIBC) represents a highly aggressive malignancy associated with significant morbidity and mortality. The current standard treatment, which includes radical cystectomy and platinum-based chemotherapy, is burdened by high toxicity and a substantial risk of relapse. For this reason, over the past decade, novel therapeutic strategies involving immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and targeted therapies have been investigated. This review aims to summarize current clinical evidence and ongoing trials evaluating these approaches in the perioperative setting. Methods: A systematic search was conducted using PubMed, EMBASE, and Cochrane databases, along with abstracts from major oncology conferences (ASCO, ESMO, SGO). Clinical trials assessing ICIs, ADCs, and targeted therapies, either alone or in combination with each other or with chemotherapy, in MIBC, were included. Results: Several early-phase and phase III trials have investigated the perioperative management of MIBC. Various studies evaluated the addition of ICIs to standard chemotherapy, demonstrating promising results in terms of pathological complete response. In parallel, the encouraging outcomes with ICIs and ADCs alone in the neoadjuvant or adjuvant setting paved the way for their combination in integrated strategies. Biomarker-driven approaches, based on circulating tumor DNA and specific genomic alterations, are being actively explored to improve patient selection and personalize treatment. Conclusions: ICIs, ADCs, and targeted therapies are reshaping the therapeutic landscape of MIBC. While early results are promising, further data and biomarker validation are essential to establish their definitive role and guide clinical decision-making in the perioperative setting. Full article

Since 1978, platinum-based drugs have benefited countless cancer patients and come to form the foundation of many cancer pharmacotherapies. These drugs induce apoptosis in cancer cells by forming cross-links between nucleobases in the DNA. Our previous studies have shown that these drugs can also interact with other similar compounds whose structures resemble nucleobases. Therefore, this study analyzed the interactions of Cisplatin, Carboplatin, and Oxaliplatin with Pyridine derivatives (Nicotinic acid, Nicotinamide, Isonicotinic acid, and Picolinic acid). These values were then compared with those for Guanine and Adenine coming from DNA using spectroscopic methods and computational chemistry (B3LYP/6-31G(d,p) and MN15/def2-TZVP methods). Theoretical studies suggest cytostatic affinity, not only for nucleobases but also for Pyridine derivatives. Experimental studies have confirmed these theoretical results. Full article

Cisplatin resistance remains a major impediment to the successful chemotherapy of various solid tumors, including ovarian, lung, and head and neck cancers. Diverse drug delivery systems with photodynamic specificity significantly target diseased cells precisely. Herein, a homogeneous photodynamic hydrogel drug-loading network based on chitosan (CS) containing zinc amino-porphyrin (ZnTAPP) has been developed for carrying cisplatin (CDDP). Aldehyde groups of glutaraldehyde acted as a bridge to connect ZnTAPP and CS. CDDP was then loaded in CS-ZnTAPP hydrogel to construct the anticancer drug system synergistically. Multiple analysis methods were applied to evaluate the chemical structure and physical properties of hydrogels, including a Fourier transform infrared spectrometer, scanning electron microscopy, an X-ray powder diffractometer, rheological measurements, etc. CS-ZnTAPP hydrogels as well as CS-ZnTAPP-CDDP hydrogels, generated abundant singlet oxygen rapidly for photodynamic therapy. Finally, the hydrogels exhibited significant anticancer activities under irradiation; the IC50 was reduced to 10.936 μg/mL toward CDDP-resistant lung cancer cells (A549/CDDP). The new hydrogel could be applied as a photodynamic anticancer drug delivery system to overcome cisplatin resistance. Full article

This review paper presents a comprehensive literature analysis that elucidates the global engagement of research teams in addressing the important problem of finding effective oncology drugs based on the following platinum group metal ions: ruthenium, rhodium and iridium. The necessity to search for new drugs can be attributed, in part, to the predominance of platinum-based chemotherapeutics in clinical practice. However, these drugs face limitations in their clinical application due to their inherent toxicity and the development of resistance by cancer cells. A distinctive attribute of these metal compounds is the formation of diamagnetic stable complexes on +II (Ru) and +III (Rh, Ir) oxidation degrees with a d⁶ electron configuration, a coordination number of six and an octahedral or pseudo-octahedral structure. In this paper we have systematised the findings presented in the literature by classifying the most significant categories of ruthenium, rhodium and iridium compounds, namely piano-stool-type arenes, polypyridine and cyclometalated complexes, dimers and multinuclear complexes. Additionally, the most crucial research challenges connected with metal complexes that have been addressed by scientists have been presented: (i) the application of prodrugs in cancer therapy; (ii) the deployment of complexes as sensitizers in PDT and PACT; (iii) the exploration of complexes as inhibitors of enzymes and biocatalysts; and (iv) the investigation of multiple-target complexes. Furthermore, the objective was to emphasise the accomplishments in this domain in recent years by identifying compounds that have entered the clinical trial phase. Full article

In recent years, several randomized controlled trials have been published regarding cervical cancer therapy and significantly changed the treatment landscape. Recent advances have improved the treatment options and allow personalized treatment concepts with escalation of treatment in high-risk disease and de-escalation with reduction in morbidity in selected low-risk patients. This review aims to provide a comprehensive analysis of the latest landmark studies that are poised to significantly influence clinical practice. Personalized treatment concepts with careful patient selection allow de-escalation in the surgical treatment of cervical cancer. In low-risk cervical cancer patients (lesions of ≤2 cm with limited stromal invasion), simple hysterectomy (SH) was non-inferior to radical hysterectomy in terms of 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention and improved sexual health and quality of life. Furthermore, sentinel lymphadenectomy is constantly replacing systematic pelvic lymphadenectomy in patients with low-risk cervical cancer. In addition, further studies are necessary to clarify the role of postoperative therapy for patients with intermediate-risk cervical cancer. Starting in 2008, the EMBRACE studies assess the role of Image guided adaptive brachytherapy (IGABT) in LACC in addition to modern external beam radiotherapy concurrent to chemotherapy. The publication of the results of the EMBRACE I prospective study established MRI guided IGABT as state-of-the-art brachytherapy for LACC. EMBRACE II and additional prospective studies emerging from this consortium will address important questions in modern radiotherapy for LACC. Immune checkpoint inhibitors (CPIs) have been evaluated across various clinical settings and are expected to be utilized in numerous scenarios due to several positive randomized trials. Particularly, the combination of platinum-based chemotherapy and pembrolizumab, with or without bevacizumab, has been established as the new standard treatment for primary metastatic or recurrent PD-L1 positive high-risk cervical cancer. In locally advanced cervical cancer, two new treatment escalation regimens—neoadjuvant chemotherapy and adjuvant CPI therapy—have been evaluated in addition to chemoradiation. Furthermore, antibody-drug conjugates, such as tisotumab-vedotin, represent a promising future therapeutic option for recurrent cervical cancer. Full article

To date, breast cancer remains one of the leading causes of death among women worldwide. Although various treatments are used in clinical settings, the efficacy and safety of such treatments are limited by tumor biology factors and patient preferences. Previous studies have shown that triple-negative BRCA1-deficient breast cancer is susceptible to DNA-damaging agents, including platinum-based drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, alone or in combination. To address whether the combinative treatment of these DNA-damaging agents can be extended to the triple-negative BRCA1-proficient breast cancer population, we investigated the anticancer activity of the well-known FDA-approved PARP inhibitor olaparib in combination with the antimetastatic ruthenium(II)–arene PTA compound RAPTA-T for triple-negative BRCA1-competent breast cancer cells (MDA-MB-468 and MDA-MB-231), with consideration of sporadic breast cancer MCF-7 cells. RAPTA-T, olaparib, and the combined agents exhibited a dose-dependent inhibition of breast cancer cell growth in selected breast cancer cells. The combination compound inhibited colony formation most effectively in MDA-MB-468 cells. Additionally, the scratch-wound assay showed that MDA-MB-468 cells migrated more slowly than MCF-7 and MDA-MB-231 cells. The results indicated that the olaparib and RAPTA-T combination can reduce or inhibit the survival, invasion, and metastasis of breast cancer cells. Moreover, the combined agents promoted apoptotic cell death, with a higher percentage of apoptosis observed in MDA-MB-468 cells than in MDA-MB-231 and MCF-7 cells. Olaparib and RAPTA-T also interfered with cell cycle progression, with the greatest inhibition observed in the S and G2/M phases of MCF-7 cells (1.6- and 3.4-fold), followed by MDA-MB-468 cells (1.6- and 1.8-fold) and MDA-MB-231 cells (1.5- and 1.4-fold). Interestingly, MDA-MB-468 cells presented the highest degree of inhibition for BRCA1 replication and BRCA1 expression. The p53, PARP, and Chk1 proteins were more strongly upregulated in MDA-MB-231 cells than in Ru-untreated control cells. Moreover, the expression levels of protein biomarkers associated with the epithelial-to-mesenchymal transition (EMT), including E-cadherin and SLUG, were remarkably reduced in all tested breast cancer cells. Together, our results show the feasibility of extending the application of PARP inhibitors beyond breast cancer with BRCA1 mutations and optimizing the combinative treatment of PARP inhibitors with antimetastasis ruthenium-based chemotherapy as new therapeutic approaches for TNBC harboring wild-type BRCA1. Full article

The significant side effects associated with platinum-based anticancer agents have driven the continuous pursuit of novel, non-platinum-based metal compounds. Ruthenium-based organometallic compounds have emerged as promising alternatives, owing to their distinctive and adaptable biochemical properties. The research efforts are focused on the development of ruthenacarborane-based anticancer drugs. The combination of ruthenium(II) complexes, recognized for their inherent anticancer potential, with carboranes, boron-rich clusters possessing unique chemical and physical characteristics, and NSAIDs, known to inhibit COX, an enzyme overexpressed in tumors, offers a novel approach for cancer therapy. Consequently, combining these three moieties into a single molecule represents a compelling strategy to develop drugs with a dual mode of action. Herein, we report the synthesis of a series of ruthenacarborane-(η⁶-p-cymene)–NSAID conjugates (4a, 4b, 5b, and 6b) by linking NSAIDs (flurbiprofen, fenoprofen, and ibuprofen) to ruthenacarborane complexes using methylene and ethylene spacers, while maintaining the integrity of the sensitive ester groups present in the system. The synthesized conjugates were thoroughly characterized using multinuclear (¹H, ¹¹B, and ¹³C) NMR spectroscopy. Notably, the conjugates demonstrated low COX inhibition and no cytotoxic potential against different cancer cell lines, probably due to oxidative deactivation confirmed by cyclic voltammetry (CV). This indicates that the conjugation of this type of ruthenacarborane with NSAIDs does not result in novel anticancer drugs. Full article

Hypopharyngeal carcinoma (HPC) represents the most prognostically unfavorable subtype among head and neck malignancies. Platinum-based neoadjuvant chemotherapy serves as a critical therapeutic approach for improving outcomes in hypopharyngeal carcinoma; however, its efficacy remains suboptimal due to the high incidence of chemoresistance. Current research on chemoresistance has primarily focused on head and neck squamous cell carcinoma (HNSCC), yet significant heterogeneity exists between hypopharyngeal carcinoma and other head and neck tumors, limiting the direct applicability of broader HNSCC research findings to hypopharyngeal carcinoma. This review systematically summarizes recent advances in understanding the mechanisms underlying chemoresistance in hypopharyngeal carcinoma, with emphasis on the comprehensive elucidation of key mechanisms, including apoptosis evasion, enhanced DNA damage repair, augmented autophagy, and increased drug efflux. Moreover, three noteworthy special scenarios involving cancer stem cells (CSCs), epithelial–mesenchymal transition (EMT), and cancer-associated fibroblasts (CAFs) are discussed. These entities not only intrinsically participate in multiple chemoresistance mechanisms but also interact synergistically, thereby further exacerbating chemoresistance in hypopharyngeal carcinoma. Full article

Triple-negative breast cancer (TNBC) accounts for about 10–15% of all breast cancers and is an aggressive disease with a poor prognosis. There is currently no standard treatment regimen for TNBC patients; thus, chemotherapy remains the main treatment. Anthracycline- and taxane-based regimens are the most widely used in a clinical setting, either alone or in combination with other chemotherapeutic agents, including poly (ADP-ribose) polymerase (PARP) inhibitors and platinum drugs. Platinum drugs have been used particularly in patients with BRCA1-mutated TNBC. Preclinical and clinical trials revealed that the response to PARP inhibition was directly correlated to the sensitivity to platinum chemotherapies. Inhibition of PARP enzymes has been shown to specifically target BRCA1 dysfunctional cells. Therefore, targeting breast cancer cells that possess genetic alterations that are absent in normal cells could be attained by the exploitation of synthetic lethality for the discovery of other candidate metals, i.e., ruthenium-derived compounds, as next-generation drugs for the treatment of TNBC. This prospective approach provides new insight into alternative treatments for breast cancers with BRCA1-associated TNBC. Full article