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.

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.

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.

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.

Gastrointestinal cancer (GIC) ranks among the most fatal malignancies globally and is characterized by a significant propensity for metastasis. While surgical intervention can effectively cure GIC in its early stages, a substantial number of cases are diagnosed at advanced stages, where the response to current therapeutic options is markedly diminished. Increasing evidence highlights the pivotal role of circadian rhythm, an intrinsic 24-hour cyclical system regulating biological activities to adapt to the alternations of day and night in the progression, metastasis, and development of chemoresistance in GIC. Recent studies have disclosed that the modulation of key circadian rhythm genes (such as BMAL1 and PER1) can suppress tumor advancement through multiple pathways. This review compiles the most recent research concerning the circadian rhythm and its influence on GIC progression. It elucidates the role of circadian genes in the initiation, metastasis, metabolism, inflammatory response, and therapeutic resistance in GIC, including both chemotherapy and targeted therapies. Furthermore, the review discusses the current implementation and future outlook of therapeutic strategies based on circadian modulation in the treatment of GIC.

Lung cancer is the second most common cancer worldwide, with persistently high morbidity and mortality rates. Despite years of research in the field, a complete cure for this disease remains elusive. Current clinical treatment options primarily include chemotherapy, surgery, and targeted drugs. However, these treatments are often limited by the highly metastatic nature of lung tumors and the development of drug resistance, resulting in suboptimal therapeutic outcomes. Ferroptosis is an iron-dependent cell death mechanism driven by lipid peroxidation, offers promising potential to overcome drug resistance in lung cancer. Recent advances in nanotechnology have enabled targeted delivery and precise regulation of ferroptosis pathways, addressing the limitations of conventional therapies. This review systematically summarizes current strategies utilizing nanomedicine to induce ferroptosis in lung cancer, with a focus on key molecular targets, such as GPX4, System Xc-, and FSP1, as well as innovative delivery platforms including metal nanoparticles, nanozymes, and responsive liposomes. Unique challenges in pulmonary drug delivery, such as mucociliary clearance and oxidative microenvironments are also discussed, along with lung cancer-specific solutions like inhalable systems and tumor microenvironment remodeling. Furthermore, we compare ferroptosis nanotherapies across different cancers to highlight the distinctive innovations in lung cancer. This article provides a comprehensive overview of recent progress and proposes optimized strategies to enhance therapeutic efficacy, offering insights into the translational potential of ferroptosis-based nanomedicine in lung cancer treatment.

Nasopharyngeal carcinoma (NPC) is a kind of malignant tumour originating from the mucosal epithelium of the nasopharynx, which has apparent regional distribution characteristics, and its incidence is increasing yearly. At present, the primary treatment method for nasopharyngeal carcinoma is radiotherapy, but radioresistance has become a complex problem to overcome to improve the therapeutic effect. Recently, ferroptosis has been proposed as a new type of iron-dependent programmed cell death, distinct from apoptosis, cell necrosis and autophagy. Many studies have shown that ferroptosis is involved in the occurrence, development, invasion and metastasis of nasopharyngeal carcinoma cells, and promoting the occurrence of ferroptosis of the same cells is a promising treatment method that should be written in the prospect. Therefore, this paper summarizes the mechanism of action of ferroptosis and its role in treating the same as above.

Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improving tumor imaging, and reducing adverse effects. With cancer responsible for millions of deaths worldwide, the development of peptide-based therapeutics offers new hope in addressing the limitations of current treatments. As detailed studies on different aspects of targeting peptides are crucial for optimizing drug development, this review provides a comprehensive overview of the literature on tumor-targeting peptides, including their structure, sources, modes of action, and their application in cancer therapy-both as standalone agents and in fusion drugs. Additionally, various computational tools for peptide-based tumor-targeting drug design and validation are explored. The promising results from these studies highlight peptides as ideal candidates for targeted cancer therapies, offering valuable insights for researchers and accelerating the discovery of novel anti-tumor peptide base drug candidates.

It is becoming increasingly clear that newer chemotherapy treatments can significantly improve long-term survival rates for cancer patients. However, it is also becoming apparent that these treatments can be associated with long-term toxicities, including the possibility of cognitive decline. a number of factors may contribute to the development of cognitive impairment in cancer patients. It would seem that the symptom complex of chemotherapy-associated cognitive dysfunction, or 'chemobrain' as it is sometimes called in the international literature, is often underdiagnosed. This is despite the fact that it is one of the leading mental health problems in patients with malignant cancer. It is of the utmost importance that this issue is recognised and that appropriate management is put in place, as chemotherapy-associated neurocognitive impairment among people with cancer has the potential to significantly impair quality of life. In our non-systematic (narrative) summary study, we aim to provide a brief overview of the clinical picture and differential diagnosis of chemotherapy-associated neurocognitive impairment, as well as an overview of the main aspects of screening and treatment. We recognise that the characteristics of the symptomatic picture and the specific course of the disease raise a number of methodological issues that may be the subject of further empirical studies.

Tumor immunotherapy, a novel and rapidly progressing cancer treatment, has experienced remarkable advancements over recent years. It focuses on augmenting the patient's immune defenses and remodeling the immune microenvironment (IME) of tumors, rather than directly targeting malignant cells. The efficacy of immunotherapy relies substantially on multiple components within the tumor microenvironment (TME), extending beyond adaptive immunity alone. Immune cells within the TME play critical roles in both promoting immune surveillance and facilitating immune evasion. This complexity emphasizes the importance of immune checkpoint regulation in immunotherapeutic interventions. Therapeutically targeting specific immune cell subsets and metabolic pathways in combination treatments can transform an immunosuppressive TME into one that is immunologically activated, facilitating enhanced immune cell infiltration and consequently improving immunotherapy efficacy. Nevertheless, comprehensive research remains necessary to fully elucidate the mechanisms underlying TME interactions and immune checkpoint regulation, ultimately enabling more effective immunotherapeutic approaches.

Drug resistance poses a significant challenge in cancer therapy, contributing to rapid recurrence, disease progression, and high patient mortality. Despite its critical impact, few reliable predictors for cancer drug response or failure have been established for clinical application. Tumor heterogeneity and the tumor microenvironment (TME) are pivotal factors influencing cancer drug efficacy and resistance. Tumor heterogeneity leads to variable therapeutic responses among patients, while dynamic interactions between cancer cells and the TME enhance tumor survival and proliferation, underscoring the urgent need to identify cellular hallmarks for predicting drug response and resistance. Single-cell and spatial omics technologies provide high-resolution insights into gene expression at the individual cell level, capturing intercellular heterogeneity and revealing the underlying pathologies, mechanisms, and cellular interactions. This review delves into the principles, methodologies, and workflows of single-cell and spatial omics in cancer drug research, highlighting key hallmarks involving tumor heterogeneity, TME reprogramming, cell-cell interactions, metabolic modulation, and signaling pathway regulation in drug treatment at single-cell and spatial levels. Furthermore, we synthesize predictive cellular biomarkers for cancer drug response and resistance across 25 cancer types, paving the way for advancements in cancer precision medicine.

Cancers originating from the same tissue vary significantly in genetic mutations and patient drug response. Furthermore, tumor tissue is composed of diverse cancer cell clones. This phenomenon, known as "cancer cell heterogeneity," occurs among tumors (between patients) and within individual tumors and is an important mechanism driving resistance to cancer therapy. Therefore, an understanding of cancer cell heterogeneity is essential for the development and delivery of more effective personalized treatments. The cancer cell lines typically used in cancer research cannot accurately replicate this heterogeneity. However, patient-derived tumor organoids (PDTOs), three-dimensional cultures of tumor cells, can precisely replicate the histological, molecular, and cellular heterogeneity of the original tumor. PDTOs generated from human cancers are now widely used as innovative tools in cancer research, including in studies of the mechanisms of cancer development and progression and in screening of anti-cancer drug. This review summarizes recent advances in human tumor research that uses PDTOs.

Long-term outcomes of patients with breast cancer have steadily improved due to advances in early detection and cancer therapeutics. Cardiovascular disease (CVD) is a leading cause of non-cancer-related mortality in this population, and this has been attributed to the cardiovascular toxicity of common breast cancer treatments including chemotherapy and radiation as well as shared risk factors between cancer and CVD. Identifying patients at risk of developing treatment-related cardiotoxicities is crucial to inform clinical decisions regarding surveillance, prevention, and management. In this review, we provide a broad overview of the treatment-related cardiotoxicities associated with common breast cancer treatment. We present data on risk-stratification tools for oncologists, including when to refer to a cardiologist, as well as recommendations for cardiovascular testing tailored to individual treatment regimens. Lastly, we review recent trial data on preventive and therapeutic approaches to treatment-related cardiotoxicities, and future directions that may lead to improved cardiovascular outcomes in this population.

Breast cancer continues to be one of the most perilous diseases globally due to the challenges in identifying cost-effective and targeted targets for effective treatment strategies. In response to these unmet demands, much research has focused on investigating the anti-breast cancer properties of natural compounds due to their multi-target modes of action and favorable safety profiles. Numerous extracts of medicinal plants, essential oils, and natural bioactive substances have exhibited anticancer properties in preclinical breast cancer models. Nonetheless, the clinical utilization of therapies based on natural chemicals is constrained by challenges such as inadequate solubility and permeability. Innovative drug delivery systems utilizing nanoparticles are currently being investigated as adaptable solutions to overcome these limitations. Polysaccharide-based nanoparticles exhibit promising biodegradability and biocompatibility, making them suitable for targeted drug delivery systems among the diverse nanocarrier types. Many polysaccharide nanocarriers, including chitosan, hyaluronic acid, cellulose, starch, and complex polysaccharides, have been shown to enhance the bioavailability and therapeutic effectiveness of phytocompounds. This review examines the anticancer properties of phytocompounds and polysaccharide nanocarriers in breast cancer before focusing on the use of polysaccharide-based nanocarriers to deliver phytocompounds for the treatment of breast cancer.

Cancer immunotherapy enhances the prognosis of cancer patients; however, it has been shown to be associated with potentially fatal cardiac risks, which requires further confirmation. This study aimed to explore the cardiotoxicity of immune checkpoint inhibitors (ICIs) in solid tumors.