Cancer remains a critical global health challenge, driven by tumor angiogenesis and immune evasion. Endostatin, a collagen XVIII-derived fragment, uniquely suppresses angiogenesis and reprograms the immunosuppressive tumor microenvironment (TME), positioning it as a dual-targeting therapeutic. Despite clinical advancements with recombinant human endostatin (rhEs), challenges such as transient efficacy and delivery limitations persist. Emerging strategies integrating nanotechnology, combination therapies, and immunomodulation (e.g., TAM reprogramming, immune checkpoint synergy) aim to amplify its therapeutic potential. This review synthesizes current knowledge on endostatin's mechanisms in angiogenesis inhibition and immune modulation. It further evaluates its clinical efficacy across solid tumors and explores innovative strategies to overcome translational barriers. By dissecting technological advancements, controversies, and synergistic opportunities with radiotherapy, chemotherapy, and immunotherapy, we aim to chart a roadmap for harnessing endostatin's full potential in redefining precision cancer therapeutics.

Natural compounds have garnered increasing interest as potential antitumor agents due to their multifaceted biological activities and relatively low toxicity profiles. This review focuses on three well-studied natural molecules: rhein, curcumin, and resveratrol, analyzing and comparing their antitumor potential across a variety of cancer models. For each compound, we present an integrated perspective encompassing natural sources, physicochemical properties, pharmacological and pharmacokinetic characteristics, and the latest in vitro and in vivo evidence of anticancer activity. Special attention is given to the molecular mechanisms underlying their antitumor effects, including the modulation of cell cycle regulators, induction of apoptosis, inhibition of metastasis and angiogenesis, and regulation of key signaling pathways such as NF-κB, PI3K/Akt/mTOR, STAT3, and MAPKs. Although numerous studies highlighted their therapeutic promise, significant barriers remain-particularly related to poor solubility and limited bioavailability-which have hindered clinical translation, especially in the case of rhein. Advances in nanotechnology-based drug delivery systems offer promising solutions to these limitations, enabling improved targeting and enhanced efficacy. This review underscores the need for continued preclinical and clinical investigations to fully elucidate the therapeutic value of these compounds and support their integration into modern oncological treatment strategies.

Non-small-cell lung cancer (NSCLC) can harbour different HER2 alterations: HER2 protein overexpression (2-35%), HER2 gene amplification (2-20%), and gene mutations (1-4%). The discovery of the HER2 gene in the 1980s raised great expectations for the treatment of several tumours. However, it was only in 2004 that HER2 mutations were identified, and they currently represent a key druggable target in NSCLC. Despite numerous strengths, there is only one FDA/EMA-approved targeted therapy, an antibody-drug conjugate (ADC) called trastuzumab deruxtecan for pretreated patients with HER2 mutant NSCLC. In the first-line treatment, the standard of care (SoC) remains chemotherapy with or without immunotherapy. In the past, pan-HER tyrosine kinase inhibitors (TKIs) were extensively studied with poor results. But, two newly developed HER2-specific TKIs with low EGFR WT inhibition (BAY2927088 and zongertinib) reported encouraging results and received the breakthrough therapy designation from the FDA. Ongoing clinical trials are investigating new agents. This review focuses on HER2 alterations. Additionally, the anti-HER2 therapies explored so far will be discussed in detail, including the following: HER2 inhibitors (pan-inhibitors and selective inhibitors), monoclonal antibodies (mAbs), and ADCs. A section of this paper is dedicated to the role of immunotherapy in HER2-altered NSCLC. The last section of this paper focuses on the drugs under development and their challenges.

Cancer remains one of the leading causes of morbidity and mortality worldwide, driving the search for innovative and selective therapeutic agents. Topoisomerases I and II are essential enzymes involved in key cellular processes such as DNA replication and transcription. They have emerged as valuable anticancer targets; thus, many inhibitors of topoisomerases have been designed and some of them are considered to be major anticancer agents such as anthracyclines, etoposide or irinotecan. A great deal of attention is currently being paid to chalcones, a class of naturally occurring compounds, since they exhibit a wide range of biological activities, including anticancer properties. These compounds are characterized by an open-chain structure and an α,β-unsaturated carbonyl moiety that enables interaction with cellular targets. Recent studies aiming to design anti-topoisomerase agents have identified both natural and synthetic chalcones, including chalcone-based hybrids. This review highlights the structural diversity of chalcones as topoisomerase inhibitors and particular attention is given to structure-activity relationship studies and molecular hybridization strategies aimed at optimizing the pharmacological profile of chalcones. These findings underline the potential of chalcones as promising scaffolds in the design of next-generation anticancer agents.

Histone deacetylases (HDACs) could regulate gene expression, arrest the cell cycle, alter epigenetics, promote angiogenesis, and evade cancer cell survival and apoptosis. HDAC inhibitors could act on cancer cells through multiple mechanisms, primarily by regulating gene expression, inducing cell-cycle arrest, promoting apoptosis, inhibiting angiogenesis, enhancing the immune response, and modifying the epigenome, representing valuable chemical entities for cancer therapy. The benzamide derivatives can chelate with the zinc ion at the active site of HDACs, interact with the surrounding amino acid residues in the active site cavity of HDACs, and cause conformational changes in HDACs. Accordingly, benzamide derivatives are useful HDAC inhibitors, and the benzamide-containing HDAC inhibitors have the potential to demonstrate robust anticancer activity. The purpose of this review is to summarize the current scenario of benzamide-containing HDAC inhibitors with anticancer therapeutic potential developed since 2020 to facilitate further rational exploitation of more effective candidates.

Daidzin (DZN), a naturally occurring isoflavone extracted from leguminous plants such as soybeans, has gained significant attention for its anticancer properties. This study provides a comprehensive overview of the pharmacokinetics (PKs), botanical sources, and therapeutic potentials of DZN, focusing on its mechanistic insights into cancer prevention and treatment. For the study, data were collected from databases such as PubMed, Google Scholar, Web of Science, and other reputable sources. In results, DZN induces oxidative stress, apoptosis, cytotoxicity, and cell cycle arrest while inhibiting proliferation, migration, invasion, and angiogenesis across various cancer cell lines, including breast, prostate, cervical, hepatocellular, and colon cancers. Its anticancer efficacy is mediated through modulation of key pathways: Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), which promotes inflammation and survival; Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), essential for proliferation and immune evasion; and Rat Sarcoma virus/Rapidly Accelerated Fibrosarcoma (RAS/RAF), a critical regulator of cell growth and chemoresistance. By inhibiting these pathways, DZN enhances apoptosis and chemotherapy sensitivity. Additionally, DZN's pharmacokinetic profile reveals favorable absorption, distribution, metabolism, and excretion (ADME) properties, with minimal toxicity in preclinical studies. Its ability to modulate pathways and enhance chemotherapy sensitivity positions DZN as a potential therapeutic candidate. Despite promising preclinical findings, the lack of clinical validation underscores the need for well-designed human trials to confirm its efficacy and safety, paving the way for its translational application in oncology.

The use of sodium-glucose cotransporter protein 2 (SGLT2) inhibitors, specifically canagliflozin and dapagliflozin, has expanded from diabetes treatment to promising anticancer applications. Epidemiological links between diabetes and certain cancers highlight the potential of these agents in oncology, as SGLT2 is highly expressed in various tumor types. By inhibiting glucose uptake, canagliflozin and dapagliflozin disrupt glycolysis-dependent tumor growth, promoting apoptosis and reducing proliferation across multiple cancer models, including liver, prostate, and lung cancers. Key pathways involved in these effects include PI3K/AKT, mTOR, and AMPK signaling. Importantly, the combination of SGLT2 inhibitors with chemotherapy or radiotherapy has been shown to enhance antitumor efficacy and reduce treatment resistance, underscoring their potential as adjunctive therapies. However, adverse effects, such as increased risk of infection, and the need for more comprehensive mechanistic studies limit current applications. Future research should focus on expanding the understanding of these mechanisms, evaluating efficacy in additional tumor types, and optimizing combination therapies to mitigate side effects. SGLT2 inhibitors thus represent a novel class of metabolic modulators with potential for significant impact in cancer therapeutics.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the beneficial and harmful effects of sorafenib, with or without co-interventions, versus placebo, no intervention, or the same co-interventions for adults, aged 18 and over, with hepatocellular carcinoma.

Cancer remains a leading global health challenge, with high mortality rates persisting despite significant advancements in therapeutic interventions. Major obstacles, including systemic toxicity, therapy resistance, metastasis, and relapses, emphasize the urgent need for safer, more effective, and readily accessible treatment strategies. Among emerging alternatives, natural bioactive compounds have gained considerable attention because of their diverse therapeutic potential and lower toxicity profiles. Urolithin A (UA), a metabolite derived from ellagic acid through gut microbiota metabolism, has emerged as a compelling anticancer agent. UA has multiple mechanisms of action, including the regulation of autophagy, enhancement of mitochondrial function, and inhibition of tumor progression and metastatic pathways. Additionally, its chemo-, immuno-, and radio-sensitization properties further increase its therapeutic advantages. Nanotechnology-driven approaches, such as nanoparticle formulations, lipids, and powder formulations, have successfully increased the solubility, stability, bioavailability, precise targeted delivery to cancer tissues, and overall therapeutic benefits of these materials. This review comprehensively explores the anticancer mechanisms of UA, its modulatory role, and advances in nanoformulation strategies, highlighting its potential as a next-generation therapeutic agent for improved cancer treatment and prevention.

In the pursuit of optimal medical care, treatment selection based on the molecular analysis of genomes, transcriptomes, and proteomes has been explored; however, this approach relies on data from large patient groups, resulting in limited accuracy in predicting treatment efficacy. Diseases involve complex pathological networks, requiring treatments that target multiple key molecules in these networks. Drug screening using these networks, which cannot be achieved through a gene expression analysis alone, requires animal models. Zebrafish embryos have an immature immune system, allowing for a high engraftment rate of human cancer cells transplanted within 48 h after fertilization. Consequently, the time required for engraftment is also reduced. Less than 500 human cancer cells are required for transplantation, enabling the assessment of drug efficacy from clinical samples within approximately 1 week. The cost of raising zebrafish is low, drug efficacy can be evaluated using small amounts of drugs, and their use aligns closely with animal welfare standards. This review aims to discuss the technical aspects of evaluating drug efficacy using zebrafish patient cancer tissue-derived xenograft (zPDX) models and summarize previous studies using zPDX as an avatar model for personalized medicine.

Several benzothiazole (BT) derivatives have recently been explored in medicinal chemistry, and they are frequently reported in the literature. The interest in this kind of heterocyclic compounds and their structural hybrids has been increasing, as shown by several reviews reported over the last decade. In this context, we found that about 70 articles related to the synthesis of BT derivatives that studied their biological activities were published in the last five years. From this, we prepared a review on the synthesis and biological activity studies about this topic. In this bibliographic review it was found that medicinal chemists also explore BT derivatives in search of anticancer and anti-Alzheimer's candidates. This review comprehends 70 articles, published between 2020 and 2024, related to the synthesis of BT derivatives with the purpose of assessing their biological activities. On the other hand, BT derivatives have been explored as molecular species that perform two or more biological actions, called multifunctional drugs. Some accounts related to the structure-activity relationship which provide a framework for drug discovery and design are also discussed. The synthetic methods of BT synthesis include the use of biocatalysts, solvent-free conditions, photocatalysts, and catalysts supported on nanoparticles. Studies also explore renewable energy sources such as microwave, UV, and visible-light and mechanochemical sources.

Cancer remains a leading global health challenge, necessitating the exploration of novel therapeutic strategies. Vitexin (apigenin-8-C-β-D-glucopyranoside), a natural flavonoid glycoside with a molecular weight of 432.38 g/mol, is derived from plants such as mung bean, beetroot, and hawthorn. This compound features a distinctive C-glycosidic bond at the 8-position of its apigenin backbone, contributing to its enhanced metabolic stability compared to O-glycosidic flavonoids. Preclinical studies demonstrate that vitexin modulates critical cellular processes such as cell cycle progression, apoptosis, autophagy, metastasis, angiogenesis, epigenetic modifications, and tumor glycolysis inhibition. It exerts its effects by targeting key signaling pathways, including phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and signal transducer and activator of transcription 3 (STAT3), and shows potential for combination therapies to enhance efficacy and overcome resistance. Advances in nanotechnology further enhance its bioavailability and delivery potential. This review comprehensively examines the current evidence on vitexin's anticancer mechanisms, highlighting its multi-target therapeutic potential and future research directions.

Stimuli-responsive silica nanoparticles have emerged as a promising platform for the targeted and controlled delivery of therapeutic agents in cancer therapy. These nanoparticles possess unique physicochemical properties that allow for the stimuli-triggered release of loaded cargos, such as drugs, enzymes, oligonucleotides, photosensitizers, and metals. The stimuli-responsive nature of these nanoparticles enables them to respond to specific internal and external signals within the tumor microenvironment, including pH, temperature, and redox potential, among others. This leads to the enhanced targeting of cancer cells and improved therapeutic efficacy while minimizing the off-target effects. This review highlights recent advances in the development and application of stimuli-responsive silica nanoparticles for the delivery of multiple active agents for cancer therapy. Overall, stimuli-responsive silica nanoparticles offer great potential for the development of more effective cancer therapies with improved selectivity and reduced side effects.

WEE1 kinase is a crucial cell cycle regulatory protein that controls the timing of mitotic entry. WEE1, via inhibition of Cyclin-dependent Kinase 1 (CDK1) and Cyclin-dependent Kinase 2 (CDK2), governs the G2-M checkpoint by inhibiting entry into mitosis. The state of balance between WEE family kinases and CDC25C phosphatases restricts CDK1/CycB activity. The WEE kinase family consists of WEE1, PKMYT1, and WEE2 (WEE1B). WEE1 and PKMYT1 regulate entry into mitosis during cell cycle progression, whereas WEE2 governs cell cycle progression during meiosis. Recent studies have identified WEE1 as a potential therapeutic target in several cancers, including therapy-resistant triple-negative breast cancer. Adavosertib's clinical promise was challenged by inter-individual variations in response and side effects. Because of these promising preclinical outcomes, other WEE1 kinase inhibitors (Azenosertib, SC0191, IMP7068, PD0407824, PD0166285, WEE1-IN-5, Zedoresertib, WEE1-IN-8, and ATRN-1051) are being developed, with several currently being evaluated in clinical trials or as an adjuvant to chemotherapies. Preclinical studies show WEE1 inhibitors induce MHC class 1 antigens and STING when given as combination therapies, suggesting potential additional therapeutic opportunities. Reliable predictors of clinical responses based on mechanistic insights remain an important unmet need. Herein, we review the role of WEE1 inhibition therapy in breast cancer.

Despite the development of a wide plethora of different anticancer agents, most of them are not used for patient treatment due to adverse effects caused by untargeted cytotoxicity. To prevent this unwanted toxicity, it is necessary to develop therapies discriminating between healthy and cancerous cells. One possible method is to target proteins overexpressed in cancer but not in normal cells. CD320 is a receptor responsible for the uptake of the transcobalamin-bound fraction of vitamin B12 (cobalamin), which is necessary for DNA synthesis, and thus, cell proliferation. CD320 was shown to be overexpressed in many cancers and its potential role as an early cancer biomarker was confirmed in several studies. Consequently, CD320 may represent a promising anti-cancer therapy target. This review summarizes the current advances and perspectives of anti-cancer CD320 targeting therapy, including therapeutic conjugates of vitamin B12, CD320-specific antibodies and nanobodies, nanoparticles loaded with cytotoxic drugs, porphyrin, and the potential of targeted CD320 therapy in attenuation of tumor tissues. Given the growing interest in CD320 as a novel target for anti-cancer therapy, further in vivo studies are required for the investigation of CD320 targeting effects on systemic cytotoxicity.

Renal cell carcinoma (RCC) accounts for about 403,000 new cases and 175,000 deaths worldwide each year. Clear cell RCC (ccRCC), the most prevalent subtype, is often driven by genetic mutations, such as VHL inactivation, leading to angiogenesis and immune escape. Immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4 have transformed treatment paradigms, yet therapeutic resistance remains a critical challenge. The immunosuppressive nature of the tumor microenvironment (TME) in ccRCC plays a central role in limiting ICI efficacy. Emerging strategies aim to overcome resistance by targeting key components of the TME, including tumor-associated macrophages, regulatory T cells (Tregs), and cytokine signaling. Agents such as nivolumab, pembrolizumab, and ipilimumab have demonstrated the ability to restore T-cell activity and mitigate immune suppression, offering clinical benefit in metastatic ccRCC. However, response rates vary, highlighting the need for rational combination therapies. ICIs combined with VEGF inhibitors have shown promising outcomes in clinical trials, and novel regimens continue to be explored. Risk stratification and personalized treatment selection are increasingly important as the therapeutic landscape evolves. This review synthesizes current advances in immunotherapy for ccRCC, with a focus on mechanisms of resistance and innovative strategies to enhance immune responsiveness. A deeper understanding of TME modulation and strategic combination approaches is essential to improve survival and quality of life for patients with advanced ccRCC.

Oleocanthal (OC), a secoiridoid phenolic compound exclusive to extra virgin olive oil (EVOO), has emerged as a promising nutraceutical with multifaceted anti-cancer properties. Despite its well-characterized anti-inflammatory and antioxidant effects, the mechanistic breadth and translational potential of OC in oncology remain underexplored and fragmented across the literature. This comprehensive review synthesizes and critically analyzes recent advances in the molecular, pharmacological, and translational landscape of OC's anti-cancer activities, providing an integrative framework to bridge preclinical evidence with future clinical application. We delineate the pleiotropic mechanisms by which OC modulates cancer hallmarks, including lysosomal membrane permeabilization (LMP)-mediated apoptosis, the inhibition of key oncogenic signaling pathways (c-MET/STAT3, PAR-2/TNF-α, COX-2/mPGES-1), the suppression of epithelial-to-mesenchymal transition (EMT), angiogenesis, and metabolic reprogramming. Furthermore, this review uniquely highlights the emerging role of OC in modulating drug resistance mechanisms by downregulating efflux transporters and sensitizing tumors to chemotherapy, targeted therapies, and immunotherapies. We also examine OC's bidirectional interaction with gut microbiota, underscoring its systemic immunometabolic effects. A major unmet need addressed by this review is the lack of consolidated knowledge regarding OC's pharmacokinetic limitations and drug-drug interaction potential in the context of polypharmacy in oncology. We provide an in-depth analysis of OC's poor bioavailability, extensive first-pass metabolism, and pharmacogenomic interactions, and systematically compile preclinical evidence on advanced delivery platforms-including nanocarriers, microneedle systems, and peptide-drug conjugates-designed to overcome these barriers. By critically evaluating the mechanistic, pharmacological, and translational dimensions of OC, this review advances the field beyond isolated mechanistic studies and offers a strategic blueprint for its integration into precision oncology. It also identifies key research gaps and outlines the future directions necessary to transition OC from a nutraceutical of dietary interest to a viable adjunctive therapeutic agent in cancer treatment.

As the most abundant fat-derived hormone, adiponectin plays an essential role in regulating energy homeostasis. Current evidence proposes the serum levels of adiponectin as a risk factor and a diagnostic/prognostic biomarker in cancer. Moreover, distinctive antineoplastic features have also been reported as a result of adiponectin supplementation in preclinical models. Mapping of the cancer-associated metabolic changes has elucidated a highly adaptable and interconnected system that allows malignant cells to sustain their growth and survival. Along with the pyruvate into acetyl-CoA conversion, downregulation of both lactate dehydrogenase and glycolysis-related genes depicts the main adiponectin-induced perturbations affecting glucose metabolism in cancer. Meanwhile, a multi-level approach involving lipid trafficking, catabolism, and de novo synthesis has been attributed to adiponectin in malignancies. The adiponectin receptor agonist AdipoRon has recently been recognized as a promising antineoplastic compound. Remarkably, AdipoRon-mediated changes in cancer metabolism occur together with its antiproliferative potential. This review aimed at recapitulating the modulatory effects of adiponectin, as well as those of its synthetic receptor agonists, in driving metabolic alterations in cancerous cells. A critical discussion is also conducted to deduce whether the adiponectin axis could serve as a putative target to address the metabolic reprogramming in cancer progression.

Cancer is a highly detrimental and fatal illness that poses a significant threat to human well-being. The pattern of cancer treatment is continuously being optimized by the advancement of old treatment approaches and the invention of novel treatment modes. Nanotechnology-based approaches are emerging as powerful candidates in the development of these advanced methods for treating tumors. This article provides a concise overview of nanotechnology for cancer or cancer nanomedicine and its applications. In light of prevalent issues, such as inadequate precision in targeting initial chemotherapy drugs, susceptibility of nucleic acid drugs to degradation, gene delivery, and the occurrence of common immune-related adverse events during immunotherapy, we explore the potential integration of nanomedicine with these treatment approaches and illustrative examples and highlight the benefits that arise from the utilization of nanomedicine.

Gastrointestinal (GI) cancers, including esophageal, gastric, pancreatic, liver, and colorectal malignancies, represent a major global health burden due to their high incidence, aggressive nature, and limited treatment outcomes. This review explores the therapeutic potential of carvacrol, a naturally occurring monoterpenoid phenol predominantly found in oregano and other aromatic plants. Carvacrol has demonstrated strong anticancer properties by modulating multiple molecular pathways governing apoptosis, inflammation, angiogenesis, and metastasis. Preclinical studies have revealed its ability to selectively target cancer cells while sparing healthy tissue. Advances in nanotechnology have further enhanced its pharmacological profile by improving solubility, stability, and tumor-targeted delivery. Additionally, carvacrol shows synergistic effects when used in combination with conventional chemotherapeutics. While the evidence is promising, clinical studies are needed to validate its translational potential. This review aims to consolidate current findings and encourage further investigation into carvacrol's application as an adjunct or alternative therapeutic agent in GI cancer management.