This network meta-analysis evaluated the efficacy of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, with or without Dexamethasone (D), for preventing chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) who were limited to these regimens.

Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, exhibits a 5-year survival rate below 10% and extremely poor clinical prognosis. Over 90% of PDAC patients harbor KRAS gene driver mutations, which promote tumor proliferation, invasion, and immunosuppression of the tumor microenvironment through constitutive activation of downstream RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways. Although the therapeutic potential of targeting KRAS has been recognized for decades, its smooth protein structure and lack of traditional drug-binding pockets led to its long-standing classification as an "undruggable" target, resulting in limited efficacy of early targeted agents. Recent breakthroughs with next-generation KRAS inhibitors have transformed the therapeutic landscape for pancreatic cancer. This review synthesizes evidence from basic research and clinical translation to provide a theoretical foundation and practical guidance for the precision treatment of KRAS-mutant pancreatic cancer.

Immune checkpoint inhibitors (ICPis) are associated with islet function impairment (IFI), manifesting as hyperglycemia, diabetes mellitus (DM), or diabetic ketoacidosis (DKA). Delayed detection and management may lead to irreversible β-cell damage and life-threatening complications. We conducted a systematic review and meta-analysis to assess the risk of IFI associated with ICPis.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, with its pathogenesis primarily linked to activating mutations in the KIT or platelet derived growth factor receptor alpha (PDGFRA) genes. Surgical resection remains the standard curative treatment for localized GIST; however, ~50% of patients eventually develop recurrence or metastasis. Since the introduction of imatinib in the early 21st century, the management of metastatic GIST has shifted from solely surgical intervention to a systemic, chronic disease management model centered on tyrosine kinase inhibitors (TKIs). However, during the course of treatment, most patients develop drug resistance. Despite the transformative impact of TKIs, some critical clinical challenges remain unresolved. Intratumoral heterogeneity, in particular, poses a significant obstacle, as tumors often comprise diverse populations of cells with varying genetic and molecular profiles. This diversity means that while some subclones may initially respond well to TKI therapy, others harboring inherent or acquired resistance mutations can continue to proliferate, ultimately leading to treatment failure. Additionally, the limited durability of TKIs responses, even in tumors initially sensitive to treatment, remains a pressing concern. Moreover, the lack of curative systemic options for advanced GIST, along with adverse drug reactions, underscores the unmet needs within this patient population. These challenges underscore the necessity of this review, which discusses current standard drug treatment strategies for advanced GIST, including sequential TKIs therapy and investigations into mechanisms of drug resistance. Finally, the review explores precise and actionable future directions for GIST drug development and clinical management, including mutation-stratified therapeutic sequencing, rational TKI-based combination regimens, and circulating tumor DNA (ctDNA)-guided real-time treatment monitoring and resistance surveillance.

Restoring apoptosis in malignant cells represents a central goal of anticancer therapy. Tumour cells often escape cell death by overexpressing anti-apoptotic members of the BCL-2 protein family, particularly BCL-2, BCL-xL, and MCL1. These proteins inhibit the intrinsic mitochondrial apoptotic pathway through intricate interactions with pro-apoptotic partners and direct modulation of the mitochondrial outer membrane. Their pivotal role in cell survival has established them as attractive therapeutic targets. Over the past two decades, significant efforts have been devoted to developing selective small-molecule inhibitors capable of neutralising these proteins and reactivating apoptosis. A first milestone was the discovery of ABT-263 (navitoclax), a dual BCL-2/BCL-xL inhibitor. Building on this achievement, the development of venetoclax, a highly selective BCL-2 inhibitor, marked a major breakthrough, demonstrating potent pro-apoptotic activity and clinical efficacy in several leukaemia subtypes. Despite these advances, the design of inhibitors of BCL-2 family members remains challenging, largely due to the structural characteristics of the BH3-binding groove, which is both shallow and hydrophobic, complicating the identification of molecules with optimal binding affinity and selectivity. PROTACs targeting BCL-xL may represent a promising future strategy, potentially overcoming the intrinsic limitations of small molecule inhibitors.

To assess the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) and identify key risk factors among adult patients.

Thalidomide represents one of the most instructive case studies in modern medicinal chemistry, embodying both a historic pharmaceutical tragedy and a remarkable example of drug repurposing and molecular reinvention. Initially introduced as a sedative and antiemetic, its catastrophic teratogenic effects reshaped global drug regulatory frameworks. Decades later, renewed investigation uncovered potent immunomodulatory, anti-inflammatory and antiangiogenic activities, leading to its controlled clinical use in erythema nodosum leprosum, multiple myeloma and related disorders. Central to this renaissance was the identification of cereblon as a key molecular target, transforming thalidomide and its analogs into versatile chemical tools for targeted protein degradation. This review provides a comprehensive overview of thalidomide from a synthetic and medicinal chemistry perspective, covering classical and modern synthetic strategies, access to analogs, stereochemical considerations and asymmetric approaches. Particular emphasis is placed on thalidomide-derived cereblon binders in PROTACs and molecular glue technologies. Beyond protein degradation, the diverse biological activities of thalidomide are discussed, including modulation of cytokines, angiogenesis, and immune signaling pathways. Collectively, thalidomide exemplifies how mechanistic insight, synthetic innovation and careful risk-benefit evaluation can transform a once-discarded molecule into a cornerstone of contemporary drug design.

ADP-ribosyltransferases (ARTs) regulate key processes in cancer, including DNA repair, transcription, immune responses, and treatment resistance. The clostridial toxin-like ADP-ribosyltransferase (ARTC) family and the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family play a crucial role in genomic stability by modification of proteins either with mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). These ARTs are promising therapeutic targets and could serve as biomarkers in cancer management. This review explores the roles of these enzymes and current knowledge on specific inhibitors. A literature search was conducted in PubMed and Google Scholar to identify studies published between 1992 and 2025 on ADP-ribosyltransferases and their roles in cancer. Among ARTC family, ART1 and ART3 modulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, influencing angiogenesis, tumor growth, and immune evasion via cluster of differentiation 8+ (CD8+) T-cell apoptosis. Within the ARTD family, poly(ADP-ribose)polymerase (PARP)1 and PARP2 are activated by DNA single-strand breaks and are clinically validated targets in cancers with homologous recombination deficiency, such as breast cancer susceptibility genes 1/2 (BRCA1/2)-mutated breast cancer. Their inhibition exemplifies synthetic lethality and has shown clinical efficacy. Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.

Vascular tumours and malformations encompass infantile hemangiomas (IHs) and genetically driven vascular malformations with distinct natural histories and therapeutic vulnerabilities. The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid malignancies, characterized by aggressive biology and a paucity of effective treatments. Activating mutations in KRAS occur in more than 90% of cases and are fundamental to tumor initiation, progression, therapeutic resistance, and immune exclusion, establishing KRAS as the dominant oncogenic driver in PDAC. Long considered undruggable, KRAS has recently become a viable therapeutic target with the development of allele-specific inhibitors as well as pan-RAS(ON) agents capable of broadly suppressing mutant RAS signaling. Preclinical models and early-phase clinical trials demonstrate meaningful antitumor activity, with emerging evidence of tumor microenvironment remodeling and delayed resistance. Combination strategies integrating KRAS-directed therapies with chemotherapy, vertical pathway inhibition, immunotherapy, and emerging approaches such as KRAS degradation and RNA-targeted approaches are being explored to improve the depth and durability of response. Together, these advances signal a paradigm shift toward molecularly guided treatment strategies in PDAC and offer a promising path forward in a disease with substantial unmet clinical need.

Oral systemic anti-cancer therapies improve convenience, but also shift responsibility for treatment management to the patient. Education, communication, and models of care must adapt to support safe, equitable, and sustainable oral anti-cancer treatment.

Chemotherapy-induced nausea and vomiting (CINV) is a common and severe adverse effect of breast cancer (BC) treatment that compromises treatment adherence and quality of life. This meta-analysis aims to assess the prevalence and risk factors of CINV in BC patients, thereby providing clinical insights for its prevention and improvement. Patient/material and methods: Relevant literature was identified through an extensive search of electronic databases from their inception up to July 10, 2025: PubMed, Web of Science, Embase, Cochrane, CNKI, Wanfang, and VIP databases on prevalence rates, odds ratios (OR), and corresponding 95% confidence intervals (CI) were extracted for analysis.

Although targeted therapy has made significant advances in cancer treatment throughout these years, drug resistance still remains a major obstacle. Plenty of evidence has proved that abnormal expression of receptor tyrosine kinase AXL is associated with targeted therapy resistance and poor clinical outcomes. AXL drives drug resistance through diverse mechanisms, including altering tumor cell phenotypes, orchestrating DNA damage response process, promoting the activation of bypass signals, or interacting with other receptor tyrosine kinases. Preclinical and clinical studies have demonstrated that combined inhibition of AXL and the other target can enhance the efficacy of various targeted therapies and improve outcomes for patients with drug resistance. This review summarizes recent advances in the specific roles of AXL in targeted therapy resistance and AXL-targeted treatment strategies. It further explores the potential clinical value of combinatorial approaches involving AXL inhibition and discusses future directions for its application in developing novel targeted therapies and advancing precision oncology treatment. 
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Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate globally, ranking among the top cancers in incidence and posing a serious human health threat. In recent years, with research advancement in traditional medicine, traditional Chinese medicine (TCM) has attracted increasing interest for its potential role in the management of hepatocellular carcinoma (HCC). As a comprehensive review, this article critically synthesizes the biological mechanisms and clinical application evidence of TCM extracts and classic formulas in HCC treatment, systematically detailing the important roles and specific mechanisms of TCM in inhibiting tumor growth, inducing apoptosis, enhancing immunity, and suppressing angiogenesis. This review aims to synthesize and analyze existing findings to provide a consolidated theoretical basis and identify potential research gaps. Furthermore, it seeks to explore new therapeutic concepts by bridging TCM theory with modern pharmacological approaches, thereby promoting the development of integrated strategies in oncology. Ultimately, we aim to contribute to the improvement of patient survival rates and quality of life. However, while preclinical evidence is promising, the clinical evidence base requires further strengthening through larger-scale, rigorously designed trials to validate efficacy and establish standardized protocols.

The emergence of drug-resistant cancers has led to the discovery of novel therapeutic agents. Medicinal plants are a promising source, with Dendrophthoe pentandra (L.) Miq. a parasitic plant used in ethnomedicine, showing promising anticancer potential. This study reviews preclinical evidence of the anticancer activity of D. pentandra, focusing on its phytochemical constituents and molecular mechanisms of action. A systematic search of Scopus and PubMed databases was conducted for preclinical studies published between 2015 and 2025. After screening, 13 articles met the eligibility criteria and were included in narrative synthesis. The 13 included studies demonstrated that D. pentandra extracts exhibit potent cytotoxic and antiproliferative effects against multiple cancer cell lines. The primary anticancer mechanism identified was the induction of apoptosis, which is frequently mediated by the upregulation of p53 and Bax proteins, downregulation of Bcl-2, and induction of cell cycle arrest at the G1/S or G2/M phase. Flavonoids, particularly quercetin, have been identified as the key bioactive phytoconstituents that contribute to these effects. In vivo studies further support these findings, showing that D. pentandra extract can inhibit tumor progression in colitis-associated cancer models by reducing inflammatory markers such as myeloperoxidase (MPO).

Although routine treatment methods aim to aggressively destroy tumour tissues, they often fail to account for the correlations of tissue destruction and regeneration processes. Despite considerable progress in the field of oncology, it is worth noting the ancient ways of treatment using products from nature which potentially can effectively support current therapies.

AKT is a critical mediator of the phosphoinositide 3-kinase (PI3K) signalling cascade, playing a key role in regulating essential cellular processes. The identification of AKT as one of the most dysregulated pathways in cancer led to the development of multiple classes of inhibitors. Despite numerous inhibitors entering clinical investigation and leading to the FDA approval of Capivasertib, an ATP-competitive AKT inhibitor, in November 2023, AKT modulation through inhibition was characterised by toxicity and poor clinical efficacy. Targeted Protein Degradation (TPD) spearheaded by PROTACs boasted a paradigmatic shift in drug discovery and was demonstrated to be a valid therapeutic alternative to modulate AKT. To date, numerous AKT-targeting PROTACs have been disclosed. The majority of them outperformed the inhibitors in suppressing AKT activity, nurturing higher potency and improved selectivity. Notably, enhanced antiproliferative effects, sustained by more robust and prolonged inactivation of the AKT downstream signalling was observed. This review highlights AKT as a central therapeutic target in oncology and focuses on AKT modulation through a targeted protein degradation approach mainly using PROTACs. The review aims at illustrating all the AKT-targeting PROTACs disclosed in literature to date, a powerful new pharmacological tool that might remarkably expand the scope of AKT-targeted therapies and further elucidate the role of AKT in both normal and cancer-related phenotypes.

Background and objectives: Therapeutic agents for cancer can cause unique pulmonary toxicities and mimic other conditions. The advent of new targeted molecular and immune therapies has changed the landscape of cancer treatment. These adverse events pose diagnostic and therapeutic challenges. This review aims to summarize the clinical presentations, radiographic patterns, and management strategies for noninfectious pulmonary complications associated with cancer therapies. Materials and methods: A literature review was conducted focusing on drug-induced lung injury (DILI), radiation-induced lung injury (RILI), pleural disease, pulmonary vascular complications, and other inflammatory conditions in patients with cancer. The data sources included clinical trials, guideline recommendations, observational studies, and expert consensus addressing incidence, pathophysiology, imaging findings, and treatment approaches. Results: Noninfectious pulmonary sequelae of anti-neoplastic therapies encompass a broad spectrum of etiologies. DILI occurs in up to 30% with variable onset and severity. The patterns can be diverse but include interstitial pneumonitis, organizing pneumonia, and diffuse alveolar damage. RILI is common and influenced by the radiation dose, volume, and concurrent therapies, and it may have both acute and chronic clinical and radiographic presentations. Pleural disease may arise from radiation and other agents, and the determination of etiology can impact management. Pulmonary vascular disease arises from many different etiologies, including therapies such as tyrosine kinase inhibitors and proteosome inhibitors, thromboembolic disease, as well as rare processes, including pulmonary veno-occlusive disease. Other conditions such as transfusion-related lung injury, cryptogenic organizing pneumonia, and interstitial lung abnormalities can also further complicate the diagnosis. Conclusions: Noninfectious pulmonary complications related to cancer therapies are diverse and often indistinguishable from infectious or malignant processes. The integration of clinical history, imaging, and selective invasive testing are needed for a timely diagnosis. Management typically involves withdrawal of the offending agent and corticosteroids, with immunosuppressive therapy reserved for severe or refractory cases. The awareness of these entities and early recognition are critical to optimizing outcomes.

As a novel form of cell death, the discovery of cuproptosis presents significant opportunities and challenges for the field of cancer therapy. Notably, polyphenolic compounds have attracted considerable research attention for their ability to induce cuproptosis. These natural compounds not only exhibit marked anti-inflammatory and antioxidant properties, but their polyhydroxy structures also enable effective chelation and transport of copper ions. This provides novel insights into cuproptosis-mediated cancer therapy. Therefore, in this review, we systematically outline copper metabolism, the mechanisms of cuproptosis, and its association with cancer, while providing an in-depth discussion of the effects and mechanisms by which polyphenolic compounds act as copper ionophores to inhibit tumor growth and progression through the induction of cuproptosis. This review indicates the promising potential of polyphenolic compounds in the field of cancer therapy and provides a theoretical basis for therapeutic strategies based on cuproptosis.

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality in the world. Although there is an armamentarium of therapeutic options available for HCC therapy, current treatment modalities still face challenges, such as limited effectiveness and resistance to therapy due to inherent intratumoral heterogeneity. Hence, the development of novel therapeutics is an unmet need. Microalgae possess the ability to provide naturally derived compounds that are attractive for biomedical applications. The multifunctional nature of microalgae, with its unique combination of anticancer metabolites, oxygen-generating capability, and photosensitizing activity, make them a versatile platform for developing next-generation cancer therapeutics. In light of the above, this succinct narrative review highlights the potential biomedical applications of microalgae in cancer therapy, with a focus on HCC. Preclinical studies have shown the significant potential of microalgae as naturally occurring sources of chemopreventive and anticancer agents against HCC. Future directions include the use of biotechnology to enhance the production of microalgal-derived bioactive compounds and the formulation of biocompatible and biodegradable drug-microalgae embolic agents with prolonged release of anticancer drugs, thereby giving rise to synergistic antitumor effects, and their application for the delivery of immune checkpoint inhibitors for immunotherapy in HCC. Overall, microalgae hold considerable promise for advancing innovative therapeutic strategies against HCC.