Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial-mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria.

Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.

Cancer immunotherapy targeting the PD-1/PD-L1 pathway has demonstrated efficacy across a range of common solid tumors and some hematopoietic malignancies. Despite these groundbreaking successes, the clinical development of other 'checkpoint inhibitors' targeting molecules like TIM-3, TIGIT, ICOS and others, has largely fallen short, often showing minimal clinical benefit even in combination with anti-PD therapy. This article explores three key hypotheses that help explain the disparity in therapeutic success: (1) the absence of tumor- specific immunosuppressive logic in many checkpoint targets, (2) the dominance-but not redundancy-of immune evasion mechanisms within the tumor microenvironment (TME), and (3) the emergence of therapy-induced resistance. This is not intended as a comprehensive review of the literature. Instead, it highlights select evidence to explain past failures and to illuminate a more strategic, biologically informed path forward.

Chitosan, a naturally derived polysaccharide, has gained considerable attention as a biomaterial for drug delivery due to its excellent biocompatibility, biodegradability, and mucoadhesive properties. However, its limited solubility and compatibility with hydrophobic drugs restrict broader applications. Recent advances in the chemical modification of chitosan specifically through fluorination have significantly improved its performance in nanomedicine. Fluorinated chitosan (FCS) exhibits enhanced hydrophobicity, chemical and thermal stability, and improved drug encapsulation efficiency, making it highly effective for cancer therapy. This review comprehensively examines the synthesis techniques of FCS nanoparticles, such as grafting, ionic gelation, and microemulsion, and evaluates how these influence particle size, stability, and drug loading. The multifunctional role of FCS in targeted cancer drug delivery, photodynamic therapy, immunotherapy, and gene editing is critically analyzed, supported by in vitro and in vivo studies demonstrating improved tumor accumulation, cellular uptake, and immune modulation. Despite its promise, FCS presents challenges such as toxicity concerns and regulatory complexities, which must be addressed for clinical translation. Future prospects include developing stimuli-responsive systems and expanding FCS applications beyond oncology. Overall, FCS represents a transformative platform in nanotechnology, offering new avenues for precision drug delivery and personalized cancer treatment.

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments.

Neoxanthin is a xanthophyll carotenoid with high-value nutritional functions for human health due to its anti-cancer, anti-oxidative, and anti-obesity activities. In this present work, we systematically reviewed the structure, source, and biosynthetic pathways of neoxanthin, and discussed the advantages and disadvantages of the prevailing extraction methods of neoxanthin. Meanwhile, this review described the latest research progress on the pharmacological activities of neoxanthin. Finally, we concluded with a discussion on the main challenges of neoxanthin production from microalgae, and proposed some future development prospects and potential solutions.

Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven total syntheses-covering five of the six members-have been reported to date. These syntheses, involving 28 to 36 steps and global yields ranging from 0.006% to 0.029%, highlight the formidable challenge these compounds present. This review summarizes the key synthetic strategies developed to access critical fragments, including the construction of the ABC diazatricyclic core and the ACE ring systems. Approaches to assembling the ABCD and ABCE tetracyclic frameworks are also discussed. Finally, we highlight the completed total syntheses of madangamines A-E, with a focus on pivotal transformations and strategic innovations that have enabled progress in this field.

Microorganisms serve as a vital source of natural anticancer agents, with many of their secondary metabolites already employed in clinical oncology. In recent years, salt-adapted microbes, including halophilic and halotolerant species from marine, salt lake, and other high-salinity environments, have gained significant attention. Their unique adaptation mechanisms and diverse secondary metabolites offer promising potential for novel anticancer drug discovery. This review consolidated two decades of research alongside current global cancer statistics to evaluate the therapeutic potential of salt-adapted microorganisms. Halophilic and halotolerant species demonstrate significant promise, with their bioactive metabolites exhibiting potent inhibitory effects against major cancer cell lines, particularly in lung and breast cancer. Evidence reveals structurally unique secondary metabolites displaying enhanced cytotoxicity compared to conventional anticancer drugs. Collectively, salt-adapted microorganisms represent an underexplored yet high-value resource for novel anticancer agents, offering potential solutions to chemotherapy resistance and treatment-related toxicity.

Selective outcome-reporting bias refers to the selective reporting of a subset of study findings. This methodological limitation may occur in cancer-related acupuncture studies, where valid empirical studies on psychometric performance are still lacking. We assessed the risk of selective outcome reporting bias in studies published in English that were included in a systematic review on acupuncture for preventing cancer chemotherapy-induced nausea and vomiting. For each study, we searched for registry availability and, if present, assessed its validity. We described each study outcome (nausea, vomiting, or both) according to the following seven items: type of outcome, domain, specific measurement, specific metric, type of data, methods of aggregation, and timepoint unit and time. Eleven studies published between 1987 and 2019 in English were evaluated. Only four (36%) had a registry, of which only two were prospective and therefore considered valid. Discrepancies were found in the specific measurement of the outcome in two studies and in the specific metric. In many other cases, discrepancies were not evaluable due to missing information. No study reported complete outcomes as planned in the published protocol. Communication about the importance of prospective trial registration, including outcome details, should be enforced to reduce the risk of selective outcome reporting bias in oncology acupuncture studies.

Chemotherapy-induced thrombocytopenia (CIT) is a common yet underrecognized complication of systemic chemotherapy, particularly in gastrointestinal (GI) cancers. Despite progress in targeted and immune-based therapies, platinum-based and fluoropyrimidine regimens, especially oxaliplatin-containing protocols, remain standard in GI cancer treatment and are linked to high rates of CIT. This complication often leads to treatment delays, dose reductions, and elevated bleeding risk. This review provides a comprehensive overview of the pathophysiology, clinical implications, and management strategies of CIT in GI malignancies. CIT arises from several mechanisms: direct cytotoxicity to megakaryocyte progenitors, disruption of the marrow microenvironment, thrombopoietin dysregulation, and immune-mediated platelet destruction. Platinum agents, antimetabolites, and immune checkpoint inhibitors can contribute to these effects. Oxaliplatin-induced CIT may occur acutely via immune mechanisms or chronically through marrow suppression. CIT affects 20-25% of solid tumor patients, with highest rates in those receiving gemcitabine (64%), carboplatin (58%), and oxaliplatin (50%). Within GI cancer regimens, FOLFOXIRI and S-1 plus oxaliplatin show higher CIT incidence compared to FOLFIRI and CAPIRI. Thrombocytopenia is graded by severity, from mild (Grade 1-2) to severe (Grade 3-4), and often necessitates treatment adjustments, transfusions, or supportive therapies. Current strategies include chemotherapy dose modification, platelet transfusion, and thrombopoietin receptor agonists (TPO-RAs) like romiplostim and eltrombopag. While platelet transfusions help in acute settings, TPO-RAs may preserve dose intensity and reduce bleeding. Emerging agents targeting megakaryopoiesis and marrow protection offer promising avenues for long-term management.

Advances in molecular diagnostics have enabled precision medicine approaches in pediatric neuro-oncology, with small-molecule drugs emerging as promising therapeutic candidates targeting specific genetic and epigenetic alterations in central nervous system (CNS) tumors. This review provides a focused overview of several small-molecule agents under investigation or in early clinical use, including ONC201, tazemetostat, vorasidenib, CDK inhibitors, selinexor, and aurora kinase A inhibitors, among others. Highlighted are their mechanisms of action, pharmacokinetic properties, early efficacy data, and tolerability in pediatric populations. Despite encouraging preclinical and early-phase results, most agents face limitations due to study heterogeneity, lack of large-scale pediatric randomized trials, and challenges in drug delivery to the CNS. The review underscores the critical need for robust prospective clinical trials for the integration of these therapies into pediatric neuro-oncology care.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but immune-related hypersensitivity reactions remain a clinical concern. Cadonilimab, a novel PD-1/CTLA-4 bispecific antibody, has demonstrated encouraging antitumor efficacy across various solid tumors; however, hypersensitivity or infusion-related reactions may occasionally occur.

Skin depigmentation or vitiligo-like depigmentation (VLD) is one of the most prevalent cutaneous adverse events during targeted therapies for cancers or autoimmune diseases. The depigmentation is usually with high mental burden and affect the disease treatment, some of which are even clinical markers for good prognosis. This study aimed to explore the underlying immunopathologic mechanisms of VLD induced by targeted therapy for cancer and autoimmune disease as well as vaccine, such as immune checkpoint inhibitors (e.g., programmed death 1/programmed death-ligand 1 and cytotoxic T-lymphocyte antigen-4 inhibitors), v-raf murine sarcoma viral oncogene homolog inhibitors, tyrosine kinase inhibitors, and other targeted agents. Additionally, it examined the clinical presentations, prognostic implications, and management strategies for VLD across oncologic and nononcologic contexts, including cases associated with vaccines and biologics. The development of VLD often correlates with improved therapeutic outcomes, but it presents unique challenges in balancing antitumor efficacy with patients' quality of life. This review integrated insights from oncology, dermatology, and immunology, and underscored the need for multidisciplinary approaches to enhance the understanding, prevention, and management of these complex cutaneous adverse events.

Cancer of the thyroid is a endocrine cancer. Although most patients achieve favorable outcomes with surgical resection, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppression therapy, a subset progresses to advanced or refractory disease. Immune checkpoint inhibitors (ICIs) blocking the PD-1/PD-L1 pathway reactivate T cells, enabling them to identify and eradicate malignant cells, thus reinstating immune surveillance against tumors. This review examines PD-L1 (Programmed Death-Ligand 1) expression in thyroid cancer, exploring its underlying regulatory mechanisms. It also discusses recent advances in PD-1/PD-L1 immune checkpoint inhibition (ICI) therapy. Furthermore, the review highlights regulatory pathways modulating PD-1/PD-L1 expression, including the mTOR pathway, androgen receptor (AR), and the CKS1B/STAT3 pathway. Notably, it summarizes recent clinical developments, such as combination regimens pairing PD-L1 blockade with mutation-targeted therapies, for which the median OS of the targeted combination therapy group was 14.7 months. This therapy has achieved the longest median OS for anaplastic thyroid carcinoma (ATC) patients so far. Additionally, the review examines innovative treatment modalities, offering a thorough synthesis of the existing state and emerging trends in PD-1/PD-L1 immunotherapies.

Melanoma is an exceptionally aggressive form of skin cancer, and its prognosis becomes dire once it metastasizes. Although substantial progress has been made in the field of immunotherapy, significant hurdles such as tumor cell immune evasion, the tumor microenvironment (TME), and immune-related adverse effects persist. Recent advancements in nanotechnology offer promising solutions to these challenges by enhancing targeting, stability, and delivery of immunotherapeutic agents. Nano-immunotherapy, which synergizes nanotechnology with immunotherapy, is evolving into a groundbreaking approach for melanoma treatment. Various nanoparticles, including liposomes, dendrimers, and polymeric nanoparticles (PNPs), are under investigation to boost immune responses, deliver immune checkpoint inhibitors (ICIs), and modulate the TME. These nanoparticles can be engineered for precise drug delivery, minimizing off-target effects and enhancing therapeutic outcomes. Moreover, the encapsulation of sensitive molecules such as cytokines, vaccines, and antibodies within nanoparticles ensures their stability and bioavailability. This review delves into the recent advancements in nano-immunotherapy for melanoma, emphasizing the mechanisms through which nanoparticles enhance immune activation and counteract the immunosuppressive TME. Additionally, we address the challenges of translating these nanomaterials into clinical settings, including optimizing nanoparticle design, ensuring safety, and achieving robust immune activation. This review provides a detailed examination of the current landscape and future potential of nano-immunotherapy as a promising strategy for melanoma treatment.

Hepatocellular carcinoma (HCC) is a malignant tumor of the liver. Treatment programs according to its physiological and pathological characteristics have reduced the number of new cases and deaths of HCC, but the morbidity and mortality are still high, posing a significant threat to human health. In recent years, the importance of mitophagy in the treatment of HCC has gradually been recognized. The activation of mitophagy inhibits the survival, proliferation and migration of HCC cells through a variety of pathways, promotes cell apoptosis, and can also reduce drug resistance, providing a new direction for the treatment of HCC. Studies have shown that Traditional Chinese medicine (TCM) monomers and their derivatives can improve the therapeutic efficacy of HCC and slow down disease progression by regulating mitophagy. This article summarizes the potential mechanism of mitophagy in the progression of HCC and comprehensively explores the potential of TCM monomers and their derivatives in the treatment of HCC, providing new perspectives and strategies for clinical treatment.

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by bone marrow infiltration, monoclonal immunoglobulin production, and multisystem damage. Proteasome inhibitors (PIs) such as bortezomib, carfilzomib, and ixazomib have significantly improved progression-free and overall survival in MM patients. However, drug resistance and adverse effects-including peripheral neuropathy and cardiotoxicity-remain major limitations to long-term disease control.

Synthetic lethality (SL) not only addresses the challenge of drug resistance associated with classical targeted therapies but also offers innovative therapeutic approaches for previously 'undruggable' targets, such as deletion mutations in tumour suppressor genes. Advances in technology have significantly enhanced our understanding of gene-gene interactions in cancer cells, enabling the identification of synthetic lethal targets and the development of drugs targeting these mechanisms. Following the extensive clinical application of PARP inhibitors-the first synthetic lethal targeted drugs approved for clinical use-emerging targets such as ATR, WEE1 and WRN have demonstrated promising clinical potential. This review examines the functions and molecular mechanisms underlying these targets and discusses recent advancements in the theory of synthetic lethality. Additionally, it emphasises the integration of synthetic lethal drugs with traditional cancer treatments, highlighting the clinical benefits of this combined strategy and its potential to facilitate more precise and individualised cancer treatment modalities in the future.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide, responsible for nearly 1.8 million deaths annually, which accounts for approximately 18.7% of global cancer-related mortality. Cisplatin, a highly effective and widely utilized anticancer drug, is particularly effective against solid tumors and serves as a cornerstone of adjuvant chemotherapy for lung cancer. Despite continuous optimization of cisplatin-based chemotherapy regimens, the emergence of cisplatin resistance frequently results in treatment failure, significantly limiting its clinical utility and therapeutic efficacy. To address this challenge, researchers have extensively investigated the biological mechanisms underlying cisplatin resistance, including impaired DNA repair pathways and inhibition of apoptosis. Among these mechanisms, epigenetic regulation-encompassing DNA methylation, histone modifications, and noncoding RNA (ncRNA) regulation-has emerged as a critical factor in mediating cisplatin resistance by modulating gene expression and signaling pathways. This review comprehensively explores the role of epigenetic mechanisms in cisplatin resistance in lung cancer, highlighting recent research findings and their potential implications for developing strategies to overcome drug resistance.

Breast cancer is the most prevalent cancer in women. Anthracyclines are commonly used as the first line of treatment, often combined with other agents, including trastuzumab. Despite their efficacy, both drugs pose a risk of cardiotoxicity, which may impair patients' quality of life (QoL) and hinder treatment persistence. Anthracycline-induced cardiotoxicity is dose-dependent and generally irreversible, whereas trastuzumab is associated with potentially reversible cardiac dysfunction. This review discusses the risk factors and biological mechanisms underlying chemotherapy-induced cardiotoxicity in breast cancer and explores effective strategies for prevention and treatment. It has been demonstrated that several cardioprotective strategies, such as treatments with angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), beta-blockers, and dexrazoxane, can help lessen cardiotoxic effects. A better understanding of cardioprotective strategies may help optimize cancer treatment without compromising cardiovascular function.