Medication-related osteonecrosis of the jaw (MRONJ), associated with antiresorptive and antiangiogenic/immunomodulatory therapies, is a severe condition affecting the jawbones. It most commonly occurs as a side effect of treatments for malignant tumors, osteological, and rheumatological diseases. Spontaneous healing is uncommon, and no definitive causal therapy exists. Surgical interventions, such as sequestrectomy or segmental resection, provide only temporary solutions, as the unpredictable involvement of the entire jawbone complicates the progression of the disease. The development of MRONJ is primarily linked to impaired bone remodeling, especially following trauma, such as tooth extractions. Patients over 65 years of age, those with weakened conditions, diabetes, ongoing steroid therapy, or poor oral hygiene are particularly affected, with the mandibular molar region being especially at risk. This study reviews the causative medications, risk factors, and the importance of early diagnosis and prevention. It also explores research directions aimed at achieving more effective treatments.

The incorporation of immune checkpoint inhibitors (ICIs) into cancer treatment has revolutionized oncology, providing marked advantages in managing various types of cancer. Nevertheless, the increasing use of ICIs has led to the emergence of immune‑related side effects, including autoimmune diseases such as inflammatory arthritis. IL‑6 signaling is crucial in the development of inflammatory arthritis and is linked to both the benefits and adverse effects of ICIs. The present review summarizes the latest progress in the IL‑6 pathway in inflammatory arthritis and discusses the therapeutic potential of IL‑6 pathway inhibitors for ICI‑induced inflammatory arthritis.

In this review, the role of microRNA‑21 (miRNA‑21) as an oncogene in lung cancer was investigated. Studies have shown that miRNA‑21 can promote the progression of lung cancer by targeting downstream target genes, and its expression can be modulated by transcription factors, DNA methylation or competitive endogenous RNA as an upstream regulator. This review highlights that miRNA‑21 can promote the progression of lung cancer through multiple signaling pathways, with a focus on the PI3K/AKT, MEK/ERK, TGF‑β/SMAD, Hippo, NF‑κB and STAT3 signaling pathways. Mechanistically, miRNA‑21 plays an important role in the progression of lung cancer by regulating multiple biological processes, such as proliferation, invasion, metastasis, apoptosis and angiogenesis in lung cancer cells. Higher expression of miRNA‑21 is associated with chemotherapy, radiotherapy and immune resistance in lung cancer. Targeting these molecular pathways may be a novel therapeutic strategy for treating lung cancer. Additionally, miRNA‑21 can serve as a biomarker for lung cancer diagnosis, prognosis and treatment response. This review also summarized the following: i) Current methods employed to inhibit the expression of miRNA‑21 in lung cancer, including CRISPR/Cas9 technology; ii) the application of natural anticancer agents, oligonucleotides, small molecules and miRNA sponges; and iii) the nano‑delivery systems developed for miRNA‑21 inhibitors. Finally, the advancements in research on miRNA mimics and inhibitors in clinical trials, which may promote the application of miRNA‑21 in clinical trials in lung cancer, were discussed. Given that lung cancer is a considerable public health challenge, these studies provide new ways of treating patients with lung cancer.

Chemotherapy-induced peripheral neuropathy (CIPN), hand-foot syndrome (HFS), and nail changes are common adverse effects associated with chemotherapy, significantly impacting the quality of life of cancer patients, and effective interventions remain an unmet need in oncologic care. Regional limb cooling is an emerging non-pharmacological approach used to prevent or reduce the severity of these adverse side effects. Although the awareness of regional limb cooling is rather prevalent, the overall use and efficacy of this non-pharmacological therapy in preventing chemotoxicities is not universally agreed upon. This paper reviews the current evidence regarding the use, efficacy, limitations, and safety of regional limb cooling in preventing or reducing CIPN, HFS, and nail changes in clinical settings.

Resveratrol is a natural compound with notable health benefits, such as anti-inflammatory, antioxidant, and chemopreventive properties. It has shown potential in inhibiting tumorigenesis and tumour progression via targeted therapy, specifically by targeting cancer stem cells (CSCs). CSCs are a small, self-renewing subpopulation within tumours that drive cancer progression and are marked by biomarker proteins such as CD133, CD44, Sox2, Nanog, Oct4, ABCG2 and ALDH1. Effective treatment requires direct targeting of these cells. Understanding the pathways that govern CSC formation and their response to resveratrol is crucial for optimizing therapy. While extensive research exists on resveratrol's effects in cancers like glioblastoma, breast, and colorectal, studies on its effects in lung cancer stem cells (LCSC) remain limited. This review aims to fill this gap by exploring resveratrol's impact on CSC across various cancers and hypothesizing its mechanisms in lung cancer stem cells (LCSC). By synthesizing findings from other cancer types, we aim to outline potential pathways resveratrol may target in lung CSC as well as to elucidate any interconnectedness between these signalling pathways.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, significantly improving outcomes for various malignancies. Despite their clinical success, only a subset of patients benefits from ICIs treatment, underscoring the need for innovative strategies to enhance their therapeutic potential. Ferroptosis, a unique form of programmed cell death driven by iron-dependent lipid peroxidation, has emerged as a promising partner for enhanced immunotherapy. Combining ferroptosis inducers with immune checkpoint blockade has shown promising potential in improving the efficacy of cancer immunotherapy. This study explores the mechanisms of ferroptosis and immune checkpoint inhibitors for synergistic cancer treatment, and reviews recent delivery platforms integrating ferroptosis and immune checkpoint blockade for enhanced therapy.

Pembrolizumab is a monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor pathway, which has increasingly been implicated in cancer treatment regimens. Since its first approval for melanoma in 2014, many trials have investigated the efficacy and safety of this new drug in different cancers. In this review, we discuss the therapeutic advances achieved with pembrolizumab in the management of eight cancers that are associated with a relatively poor prognosis. We also report the FDA approvals of this drug, highlighting promising ongoing trials and potential aspects for future research.

Immune checkpoint inhibitors targeting negative regulatory checkpoints including programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 have produced significant improvements in progression-free survival (PFS) and overall survival in multiple solid tumors. Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that is highly expressed by exhausted T cells. Dual blockade of LAG-3 and PD-1 with monoclonal antibodies relatlimab and nivolumab has improved PFS in advanced melanoma, leading to Food and Drug Administration approval for this indication. Concurrently, enthusiasm for targeting LAG-3 has been tempered by negative results in multiple indications, although novel approaches including LAG-3-directed bispecifics tebotelimab continue to demonstrate promise. In this review, we discuss the current understanding of LAG-3 in regulating antitumor immunity and the ongoing state of clinical development of LAG-3-directed agents in cancer.

With the rapid introduction of novel breast cancer therapies, recognizing and managing side effects is essential to maintain adherence and improve outcomes. As novel oral endocrine therapies and combination strategies including targeted agents have prolonged progression and in some cases disease-free survival, early recognition and appropriate management of these toxicities is critical to optimize quality of life. Dermatologic adverse events are frequently associated with novel breast cancer therapies including immune checkpoint inhibitors (ICIs), targeted therapies, and antibody-drug conjugates (ADCs). These include various rashes, stomatitis, and alopecia, necessitating multidisciplinary dermatologic intervention to allow for prompt management of cutaneous toxicities and continuation of oncologic therapy. Targeted breast cancer therapies, including ADCs, can also induce ocular adverse events (OAEs), such as corneal pseudomicrocysts which lead to blurry vision and eye pain. Current preventative therapies have had limited success for these OAEs, necessitating dose interruptions. Although anthracycline-based chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy are associated with an increased risk of heart failure and left ventricular (LV) dysfunction, novel breast cancer therapies including ADCs, HER2 tyrosine kinase inhibitors, cyclin-dependent kinase 4 and 6 inhibitors, ICIs, and oral selective estrogen receptor degrader are also associated with an increased risk of LV dysfunction, heart failure, corrected QT prolongation, myocarditis, and bradycardia. This review provides a comprehensive overview of novel and emerging breast cancer therapy toxicities, with suggested management strategies to prevent and mitigate these adverse events. Through a multidisciplinary approach involving preventative strategies, monitoring, proactive interventions, providers can minimize symptom burden and improve patient adherence, ultimately improving breast cancer outcomes.

The search for novel anticancer agents has brought carbonic anhydrase (CA) isoforms IX and XII into focus due to their critical role in tumor growth and survival, particularly under hypoxic conditions. These tumor-associated enzymes regulate pH and ion transport in cancer cells, making them attractive therapeutic targets. Among the compounds explored as CA inhibitors, 1,2,3-triazoles stand out for their versatile CA inhibition potential and favorable pharmacokinetic properties. 1,2,3-triazole scaffold, easily synthesized via click reactions, offers a promising framework for developing selective inhibitors against CA IX and XII. Recent research highlights the anticancer potential of 1,2,3-triazole derivatives, which selectively inhibit these isoforms, impairing tumor microenvironment regulation and thus enhancing cancer treatment efficacy. The present review explores the structure-activity relationships (SAR) of 1,2,3-triazole scaffolds as tumor-associated CA IX and XII inhibitors. We provide insights into their design and therapeutic potential by examining key structural modifications that enhance potency and selectivity. This comprehensive analysis aims to guide the future development of 1,2,3-triazole-based CA inhibitors for use as antitumor agents.

Chemotherapy, as one of the main treatments for patients with colorectal cancer (CRC), brings clinical benefits with varying degrees of gastrointestinal reactions. Post-chemotherapy diarrhea is one of the factors affecting the quality of life of cancer patients. In severe cases, it can cause interruption of the chemotherapy process and even be life-threatening. Probiotics' role in preventing post chemotherapy diarrhea in CRC patients has not been proven.

Immunotherapies, particularly immune checkpoint inhibitors (ICIs), have revolutionized cancer clinical management, but low response rates and treatment resistance remain challenging. Protein post-translational modifications (PTMs) are critical for governing protein expression, localization, functions, and interactions with other cellular molecules, which notably build up the diversity and complexity of the proteome. A growing body of evidence supports that PTMs influence immunotherapy efficacy and outcomes by post-translationally modulating the expression and functions of immune checkpoints. Therefore, understanding the PTM mechanisms that govern immune checkpoints is paramount for developing novel treatment strategies to improve immunotherapy efficacy and overcome resistance. This review provides an overview of the current comprehension of the regulatory mechanisms by which PTMs (glycosylation, phosphorylation, ubiquitination, acetylation, succinylation, palmitoylation, lactylation, O-GlcNAcylation, UFMylation, and neddylation) modulate immune checkpoints to unveil potential therapeutic targets. Moreover, this review discusses the potential of therapeutic strategies targeting PTMs of immune checkpoints, providing insights into the combination treatment with ICIs in maximizing the benefits of immunotherapy and overcoming resistance.

Aberrant Wnt signaling is a hallmark of many cancers, driving proliferation and disease progression. This review provides a focused overview of recent research (past 10-15 years) into Wnt inhibitors as potential cancer therapeutics, emphasizing their diverse mechanisms of action at the molecular level. We examine the latest findings regarding Wnt ligand blockade, frizzled receptor antagonism, and downstream pathway modulation, assessing each approach's clinical potential and challenges. This includes a discussion of combination therapies and strategies to overcome resistance. Ultimately, this review aims to provide a clear and concise understanding of the current landscape of Wnt inhibition, guiding future research toward more precise and effective cancer treatments.

Combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs (AADs) holds promise in cancer treatment. While ICIs block signals that help cancer cells evade the immune system, anti-angiogenic agents target blood vessels, limiting tumor growth by restricting nutrient and oxygen supplies. Additionally, the judicious use of AADs can normalize the tumor vasculature, alleviate hypoxia, and enhance the antitumor immune response. As the shutdown of a single target does not necessarily eradicate cancer, the use of combinations of molecular-targeted agents has been proposed, and some pioneering research has been conducted to examine the efficacy of this strategy. The combination of these two modalities offers a synergistic approach, enhancing the efficacy of tumor eradication. Recent studies have elucidated the rationale behind this combination therapy, but a limited response rate has been achieved with monotherapy. Clinical trials have demonstrated the potential of this combination, with improved outcomes in various solid tumor types. The dual blockade of angiogenesis and immune checkpoints is poised to become a standard of care, with indications expected to expand as more evidence accumulates. The antitumor efficacy of current therapies is limited, most likely because of the high degree of cancer clonal heterogeneity, intratumor genetic heterogeneity, and cell signal complexity. Although numerous studies have been conducted in this area, this review provides a comprehensive analysis of the molecular rationale for ICIs and AADs in cancer therapy. We not only compare the individual properties and mechanisms of both treatments, but also explore their complementary roles, which are essential for optimizing personalized treatment strategies. By addressing key challenges such as tumor heterogeneity, immune evasion, and resistance to monotherapies, we demonstrate how this combination approach can enhance treatment outcomes. Furthermore, we incorporate the latest preclinical and clinical findings and offer future perspectives on optimizing drug selection, dosing, and treatment design to maximize therapeutic efficacy.

The integration of artificial intelligence (AI) into oncology drug discovery is redefining the traditional pipeline by accelerating discovery, optimizing drug efficacy, and minimizing toxicity. AI has enabled groundbreaking advancements in molecular modeling, simulation techniques, and the identification of novel compounds, including anti-tumor and antibodies, while elucidating mechanisms of drug toxicity. Additionally, AI has emerged as a critical tool in precision medicine, driving the formulation and release of targeted therapies and improving the development of treatments for oncology and central nervous system diseases. Furthermore, AI-assisted clinical trial designs have further optimized the recruitment and stratification of patients, reducing the time and cost of trials. Despite these advancements, challenges such as data integration, transparency, and ethical considerations persist. By synthesizing current innovations, this manuscript provides a comprehensive analysis of AI-driven approaches in drug discovery and their potential to advance oncology therapeutics and precision medicine. It examines the transformative role of AI across the drug development continuum, with a focus on its applications in computer-aided drug design (CADD), generative artificial intelligence (GAI), and high-throughput screening (HTS).

The treatment of cancer remains a formidable challenge, largely due to the difficulty in achieving efficient co-delivery of chemotherapeutic and immunotherapeutic agents to specific tumor sites. Nanosuspension-based biomaterial drug delivery systems for anti-cancer (NBDDSC) have emerged as promising platforms for enhancing drug solubility, stability, and targeted delivery. These systems can be categorized into natural polymer-based, synthetic polymer-based, and hybrid nanosuspensions, each offering distinct advantages in biocompatibility, drug loading, and controlled release. However, the majority of existing NBDDSC rely on synthetic materials that function primarily as excipients, offering no intrinsic therapeutic value. These materials often require intricate manufacturing processes, which can result in issues with batch consistency, reduced stability, and diminished therapeutic efficacy. Additionally, the potential side effects associated with synthetic components further underscore the limitations of these systems. This review explores various preparation methods for nanosuspensions, including antisolvent precipitation, high pressure homogenization, and ultrasonication, highlighting their impact on particle size, drug encapsulation, and stability. Furthermore, the targeted applications of these nanosuspensions in treating of cancers such as glioma is discussed to emphasize their potential clinical relevance. By addressing current limitations, this review underscores the critical importance of simpler, safer, and clinically translatable NBDDSC in advancing cancer therapy.

Doxorubicin (DOX) is an anthracycline chemotherapeutic agent widely used for treating various malignancies due to its remarkable efficacy. However, the dose-limiting cardiotoxicity induced by DOX remains a critical clinical concern with limited therapeutic strategy. Several molecular mechanisms underlying the pathogenesis of doxorubicin-induced cardiotoxicity (DIC) have been proposed, including oxidative stress, dysregulation of Top2β, mitochondrial damage, imbalance of calcium homeostasis, ferroptosis, and inflammatory responses. Increasing studies have posed the promise of the natural products flavonoids against DIC attributed to its advantages in antioxidant activity as well as anti-cancer properties. This paper reviews relevant publications to date and comprehensively summarizes the evidence from preclinical and clinical studies in support of the cardioprotective effect of seven flavonoids subclasses against DIC, including flavones with 18 compounds, flavonols with 11 compounds, isoflavones with 7 compounds, flavanones with 6 compounds, chalcones with 3 compounds, flavanols with 2 compounds and anthocyanins with 2 compounds. Specially, several lines of evidence have also demonstrated the anti-cancer property of flavonoids in addition to the cardioprotective property. This review synthesizes comprehensive mechanistic and translational insights to inform future preclinical and clinical investigations aiming at integrating flavonoid-based interventions into oncotherapeutic regimens. The accumulated evidence underscores flavonoids as promising candidates for DIC as well as adjuvant cancer therapy.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block inhibitory pathways that cancer cells exploit to suppress T-cell activation. Although immune-related adverse events (irAEs) linked to ICI therapy are well documented and encompass dermatologic, endocrine, gastrointestinal, hepatic, and neurologic systems, ICI-related dysautonomia remains a rare phenomenon. Management of ICI-related dysautonomia is undefined.

Selenium, an essential micronutrient in the human body, not only exhibits potent antioxidant properties but also plays a critical role in regulating thyroid hormone metabolism, maintaining normal immune function, and inhibiting tumour progression. Among selenium-containing compounds, ebselen is the most extensively studied drug candidate. Research has shown that various derivatives obtained through structural modifications of Ebselen exhibits significant biological activities; however, these compounds have yet to progress to clinical trials. Consequently, selenium-containing heterocyclic compounds represent a promising avenue for drug discovery and development. This review summarizes three synthetic approaches for constructing selenium-containing heterocyclic compounds and emphasizes their notable biological activities and potential applications in pharmaceuticals.

Recent advances in molecular genetic research, driven by the development of genomic analysis technologies, have significantly improved treatment outcomes for leukemia. In recent years, mounting evidence indicates that germline genetic background influences drug sensitivity and the risk of adverse effects, underscoring the growing importance of personalized treatment strategies. In particular, the NUDT15 polymorphism, which determines sensitivity to 6-mercaptopurine, has garnered significant attention. Notably, a low-activity variant of this polymorphism, prevalent in Asian countries, has been shown to substantially increase the risk of bone marrow suppression and other adverse effects. Pre-treatment analysis of the NUDT15 polymorphism has demonstrated utility in dose adjustment, helping to mitigate the risk of treatment-related toxicities. Studies have also explored the relationship between genetic background and late complications of leukemia treatment. Optimization of therapeutic strategies based on pharmacogenetic insights holds promise for minimizing complications while maximizing treatment efficacy for each individual patient.