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Previous studies have demonstrated that genetic alterations governing epigenetic processes frequently drive tumor development and that modifications in RNA may contribute to these alterations. In the 1970s, researchers discovered that N6-methyladenosine (m6A) is the most prevalent form of RNA modification in advanced eukaryotic messenger RNA (mRNA) and noncoding RNA (ncRNA). This modification is involved in nearly all stages of the RNA life cycle. M6A modification is regulated by enzymes known as m6A methyltransferases (writers) and demethylases (erasers). Numerous studies have indicated that m6A modification can impact cancer progression by regulating cancer-related biological functions. Tumor angiogenesis, an important and unregulated process, plays a pivotal role in tumor initiation, growth, and metastasis. The interaction between m6A and ncRNAs is widely recognized as a significant factor in proliferation and angiogenesis. Therefore, this article provides a comprehensive review of the regulatory mechanisms underlying m6A RNA modifications and ncRNAs in tumor angiogenesis, as well as the latest advancements in molecular targeted therapy. The aim of this study is to offer novel insights for clinical tumor therapy.

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Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy. Prior research has illuminated reasons behind drug resistance, including increased drug efflux, alterations in drug targets, and abnormal activation of oncogenic pathways. However, there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment (TME). Recent studies on extracellular vesicles (EVs) have provided valuable insights. EVs are membrane-bound particles secreted by all cells, mediating cell-to-cell communication. They contain functional cargoes like DNA, RNA, lipids, proteins, and metabolites from mother cells, delivered to other cells. Notably, EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs. This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance, covering therapeutic approaches like chemotherapy, targeted therapy, immunotherapy and even radiotherapy. Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance. Additionally, targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance. We highlight the importance of conducting in-depth mechanistic research on EVs, their cargoes, and functional approaches specifically focusing on EV subpopulations. These efforts will significantly advance the development of strategies to overcome drug resistance in anti-tumor therapy.

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Upconverted UCNPs@mSiO2-NH2 nanoparticles were synthesized via thermal decomposition while employing the energy resonance transfer principle and the excellent near-infrared (NIR) light conversion property of up-conversion. The 808 nm NIR-excited photocontrolled nitric oxide (NO) release platform was successfully developed by electrostatically loading photosensitive NO donor Roussin's black salt (RBS) onto UCNPs@mSiO2-NH2, enabling the temporal, spatial, and dosimetric regulation of NO release for biological applications of NO. The release of NO ranged from 0.015⁓0.099 mM under the conditions of 2.0 W NIR excitation power, 20 min of irradiation time, and UCNPs@mSiO2-NH2&RBS concentration of 0.25⁓1.25 mg/mL. Therefore, this NO release platform has an anti-tumor effect. In vitro experiments showed that under the NIR light, at concentrations of 0.3 mg/mL and 0.8 mg/mL of UCNPs@mSiO2-NH2&RBS, the activity of glioma (U87) and chordoma (U-CH1) cells, as measured by CCK8 assay, was reduced to 50 %. Cell flow cytometry and Western Blot experiments showed that NO released from UCNPs@mSiO2-NH2&RBS under NIR light induced apoptosis in brain tumor cells. In vivo experiments employing glioma and chordoma xenograft mouse models revealed significant inhibition of tumor growth in the NIR and UCNPs@mSiO2-NH2&RBS group, with no observed significant side effects in the mice. Therefore, NO released by UCNPs@mSiO2-NH2&RBS under NIR irradiation can be used as a highly effective and safe strategy for brain tumor therapy.

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Depression is a common occurrence among cancer patients, and it significantly impacts their clinical outcomes and quality of life, with a high incidence during anti-tumor treatment or after surgery. The association between surgery and depression is the result of the interaction of various factors, including physiological, psychological, and social factors, all of which are intertwined and make patients susceptible to depression after surgical treatment. Postoperative depression has a significant negative impact on many aspects of cancer patients, and it requires timely identification and intervention to improve the overall outcome.

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As a developing radiation treatment for tumors, neutron capture therapy (NCT) has less side effects and a higher efficacy than conventional radiation therapy. Drugs with specific isotopes are indispensable counterparts of NCT, as they are the indespensable part of the neutron capture reaction. Since the creation of the first and second generations of boron-containing reagents, NCT has significantly advanced. Notwithstanding, the extant NCT medications, predominantly comprised of small molecule boron medicines, have encountered challenges such monofunctionality, inadequate targeting of tumors, and hypermetabolism. There is an urgent need to promote the research and development of new types of NCT drugs. Bio-nanomaterials can be introduced into the realm of NCT, and nanotechnology can give conventional medications richer functionality and significant adaptability. This can complement the advantages of each other and is expected to develop more new drugs with less toxicity, low side effects, better tumor targeting, and high biocompatibility. In this review, we summarized the research progress of nano-drugs in NCT based on the different types and sources of isotopes used, and introduced the attempts and efforts made by relevant researchers in combining nanomaterials with NCT, hoping to provide pivotal references for promoting the development of the field of tumor radiotherapy.

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Tumor cells achieve their adaptability through various metabolic reprogramming processes. Among them, ammonia, as a traditional metabolic waste, plays an increasingly important role in the tumor microenvironment along with its associated metabolites. Other cells in the microenvironment can also reshape the immune status of the microenvironment by regulating ammonia-related metabolism, and targeting this metabolic aspect has emerged as a potential strategy for tumor treatment. In this study, we have systematically reviewed the source and destination of ammonia in tumor cells, as well as the links between ammonia and other biological processes. We have also analyzed the ammonia-related metabolic regulation of other cells (including T cells, macrophages, dendritic cells, natural killer cells, myeloid-derived suppressor cells, and stromal cells) in the tumor microenvironment, and summarized the tumor treatment methods that target this metabolism. Through ammonia-related metabolic reprogramming, tumor cells obtain the energy they need for rapid growth and proliferation. Multiple immune cells and stromal cells in the microenvironment also interact with each other through this metabolic regulation, ultimately leading to immune suppression. Despite the heterogeneity of tumors and the complexity of cellular functions, further research into therapeutic interventions targeting ammonia-related metabolism is warranted. This review has focused on the role and regulation of ammonia-related metabolism in tumor cells and other cells in the microenvironment, and highlighted the efficacy and prospects of targeted ammonia-related metabolism therapy.

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Carcinoembryonic antigen (CEA) is a tumor-associated antigen primarily produced by tumor cells. It has been implicated in various biological processes such as cell adhesion, proliferation, differentiation, and metastasis. Despite this, the precise molecular mechanisms through which CEA enhances tumor cell proliferation remain largely unclear. Our study demonstrates that CEA enhances the proliferation and migration of non-small cell lung cancer (NSCLC) while also inhibiting cisplatin-induced apoptosis in NSCLC cells. Treatment with CEA led to an increase in mitochondrial numbers and accumulation of lipid droplets in A549 and H1299 cells. Additionally, our findings indicate that CEA plays a role in regulating the fatty acid metabolism of NSCLC cells. Inhibiting fatty acid metabolism significantly reduced the CEA-mediated proliferation and migration of NSCLC cells. CEA influences fatty acid metabolism and the proliferation of NSCLC cells by activating the PGC-1α signaling pathway. This regulatory mechanism involves CEA increasing intracellular cAMP levels, which in turn activates PKA and upregulates PGC-1α. In NSCLC, inhibiting the PKA-PGC-1α signaling pathway reduces both fatty acid metabolism and the proliferation and migration induced by CEA, both in vitro and in vivo. These results suggest that CEA contributes to the promotion of proliferation and migration by modulating fatty acid metabolism. Targeting CEA or the PKA-PGC-1ɑ signaling pathway may offer a promising therapeutic approach for treating NSCLC.

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Protein degraders, emerging as a novel class of therapeutic agents, have gained widespread attention due to their advantages. They have several advantages over traditional small molecule inhibitors, including high target selectivity and ability to target "undruggable" targets and overcome inhibitor drug resistance. Tremendous research and development efforts and massive investment have resulted in rapid advancement of protein degrader drug discovery in recent years. Here, we overview the latest clinical and preclinical updates on protein degraders presented at the 2023 ASH Annual Meeting.

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The dry root of the soybean plant Astragalus membranaceus (Fisch) Bge. var. mongholicus (Bge) Hsiao or A. membranaceus (Fisch) Bge, Astragali Radix (AR) has a long medicinal history. Astragalus polysaccharide (APS), the natural macromolecule that exhibits immune regulatory, anti-inflammatory, anti-tumor, and other pharmacological activities, is an important active ingredient extracted from AR. Recently, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosis. In addition, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body's immunity. This macromolecule has prospects for broad application in tumor therapy through various pathways. In this article, we present the latest progress in the research on the anti-tumor effects of APS and its underlying mechanisms, aiming to provide novel theoretical support and reference for its use in cancer therapy.

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Introduction: Spatiotemporally controlled release of siRNA for anti-tumor therapy poses significant challenges. Near-infrared (NIR) light, known for its exceptional tissue penetration and minimal tissue invasiveness, holds promise as a viable exogenous stimulus for inducing controlled siRNA release in vivo. However, the majority of light-responsive chemical bonds exhibit absorption wavelengths in the ultraviolet (UV) or short-wavelength visible light range. Methods: To achieve NIR-controlled siRNA release, the study synthesized a UV-sensitive triblock copolymer cRGD-poly(ethylene glycol)-b-poly(aspartic acid ester-5-(2'-(dimethylamino)ethoxy)-2-nitrobenzyl alcohol)-b-polyphenylalanine, abbreviated as cRGD-PEG-PAsp(EDONB)-PPHE. This copolymer is composed of a cRGD-capped PEG block (cRGD-PEG), a poly(aspartate) block modified with cationic moieties through UV-cleavable 2-nitrobenzyl ester bonds [PAsp(EDONB)], and a hydrophobic polyphenylalanine block (PPHE). The cationic amphiphilic polymer cRGD-PEG-PAsp(EDONB)-PPHE can assemble with hydrophobic upconversion nanoparticles (UCNPs) to form a cationic micelle designated as T-UCNP, which subsequently complexes with siRNA to create the final nanopolyplex T-si/UCNP. siRNA-PLK1 was employed to prepare T-PLK1/UCNP nanopolyplex for anti-tumor therapy. Results: T-PLK1/UCNP not only exhibited outstanding tumor cell targeting through cRGD modification but also achieved 980 nm NIR-controlled PLK1 gene silencing. This was achieved by utilizing the encapsulated UCNPs to convert NIR into UV light, facilitating the cleavage of 2-nitrobenzyl ester bonds. As a result, there was a significant suppression of tumor growth. Conclusion: The UCNPs-encapsulated nanopolyplex T-si/UCNP, capable of co-delivering siRNA and UCNPs, enables precise NIR-controlled release of siRNA at the tumor site for cancer RNAi therapy. This nanopolyplex can enhance the controllability and safety of RNAi therapy for tumors, and it also holds the potential to serve as a platform for achieving controlled release and activation of other drugs, such as mRNA and DNA.

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Self-healing hydrogels have shown great application potential in drug delivery for anti-tumor therapy and tissue engineering. In this research, Doxorubicin (DOX) was coupled onto the oxidized pectin (pec-Ald) to prepare DOX grafted pec-AD and used to fabricate self-healing hydrogel for lung cancer therapy combined with novel herbal medicine extract limonin targeting lung cancer cells. The hydrogel was prepared with P(NIPAM195-co-AH54) cross-linking and the hydrazone bond cross-linked hydrogel showed good mechanical property and self-healing behavior. With pectin composition, the hydrogel was still biodegradable catalyzed by enzyme and in vivo. The hydrogel formed fast fit for injectable application and the hydrogel itself showed moderate lung cancer inhibition activity. With limonin loading, the hydrogel showed synergistic lung cancer therapy with the tumor growth greatly inhibited. The covalent coupling of DOX and loaded limonin in the hydrogel decreased in vivo toxicity and the hydrogel degraded on time. With biodegradability and improved lung cancer therapy efficiency, this DOX grafted self-healing hydrogel could find great potential application in cancer therapy in near future.

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[Objective]To summarize Professor SHU Qijin's academic experience in diagnosing and treating salty taste in the mouth after anti-tumor therapy.[Methods]Through learning from teacher in outpatient,reading ancient books and analyzing the medical records,this paper arranged Professor SHU's medical records of salty taste in the mouth after anti-tumor therapy and introduced his clinical experience in treating that from following aspects:etiology and pathogenesis,principles and laws of treatment,and provided one medical case as evidence.[Results]Professor SHU believes that salty taste in the mouth after anti-tumor therapy is closely related to overgrowth of the kidney fluid due to the imbalance of Yin and Yang and dampness caused by unrestriction of water-liquid metabolism of the kidney and spleen,and briefly summarizes the treatment principles in three aspects:reconciling and replenishing Yin and Yang of the kidney,invigorating the spleen and eliminating dampness.The attached medical record was identified as fire excess from Yin deficiency and damp abundance.Professor SHU treated the case by nourishing Yin and reducing fire as well as invigorating the spleen and eliminating dampness,modified Zhibai Dihuang Pill and Pingwei Powder was used for treatment and good results were achieved.[Conclusion]In the treatment of salty taste in the mouth after anti-tumor therapy,Professor SHU adheres to comprehensive analysis by the four examination methods and advocates flexible syndrome differentiation.Professor SHU's academic experience is rich and clinical curative effect is remarkable.Summarizing his medication characteristics has high guiding significance for the clinical application.

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Metabolic reprogramming, especially reprogrammed glucose metabolism, is a well-known cancer hallmark related to various characteristics of tumor cells, including proliferation, survival, metastasis, and drug resistance. Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway (PPP), a branch of glycolysis, that converts glucose-6-phosphate (G6P) into 6-phosphogluconolactone (6PGL). Furthermore, PPP produces ribose-5-phosphate (R5P), which provides sugar-phosphate backbones for nucleotide synthesis as well as nicotinamide adenine dinucleotide phosphate (NADPH), an important cellular reductant. Several studies have shown enhanced G6PD expression and PPP flux in various tumor cells, as well as their correlation with tumor progression through cancer hallmark regulation, especially reprogramming cellular metabolism, sustaining proliferative signaling, resisting cell death, and activating invasion and metastasis. Inhibiting G6PD could suppress tumor cell proliferation, promote cell death, reverse chemoresistance, and inhibit metastasis, suggesting the potential of G6PD as a target for anti-tumor therapeutic strategies. Indeed, while challenges-including side effects-still remain, small-molecule G6PD inhibitors showing potential anti-tumor effect either when used alone or in combination with other anti-tumor drugs have been developed. This review provides an overview of the structural significance of G6PD, its role in and regulation of tumor development and progression, and the strategies explored in relation to G6PD-targeted therapy.

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Background: The CRISPR/Cas13a system offers the advantages of rapidity, precision, high sensitivity, and programmability as a molecular diagnostic tool for critical illnesses. One of the salient features of CRISPR/Cas13a-based bioassays is its ability to recognize and cleave the target RNA specifically. Simple and efficient approaches for RNA manipulation would enrich our knowledge of disease-linked gene expression patterns and provide insights into their involvement in the underlying pathomechanism. However, only a few studies reported the Cas13a-based reporter system for in vivo molecular diagnoses. Methods: A tiled crRNA pool targeting a particular RNA transcript was generated, and the optimally potential crRNA candidates were selected using bioinformatics modeling and in vitro biological validation methods. For in vivo imaging assessment of the anti-GBM effectiveness, we exploited a human GBM patient-derived xenograft model in nude mice. Results: The most efficient crRNA sequence with a substantial cleavage impact on the target RNA as well as a potent collateral cleavage effect, was selected. In the xenografted GBM rodent model, the Cas13a-based reporter system enabled us in vivo imaging of the tumor growth. Furthermore, systemic treatments using this approach slowed tumor progression and increased the overall survival time in mice. Conclusions: Our work demonstrated the clinical potential of a Cas13a-based in vivo imaging method for the targeted degradation of specific RNAs in glioma cells, and suggested the feasibility of a tailored approach like Cas13a for the modulation of diagnosis and treatment options in glioma.

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For decades, immunotherapies have offered hope for patients with advanced cancer. However, they show distinct benefits and limited clinical effects. Tumor vaccines have the potential to prime tumor-antigen-specific T cells and induce broad subsets of immune responses, ultimately eradicating tumor cells. Here, we classify tumor vaccines by their anti-tumor mechanisms, which include boosting the immune system, overcoming tumor immunosuppression, and modulating tumor angiogenesis. We focus on multidimensional tumor vaccine strategies using combinations of two or three of the above mechanisms, as these are superior to single-dimensional treatments. This review offers a perspective on tumor vaccine strategies and the future role of vaccine therapies in cancer treatment.

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Angiogenesis is the process of generating new blood vessels from pre-existing vasculature. Under normal conditions, this process is delicately controlled by pro-angiogenic and anti-angiogenic factors. Tumor cells can produce plentiful pro-angiogenic molecules promoting pathological angiogenesis for uncontrollable growth. Therefore, anti-angiogenic therapy, which aims to inhibit tumor angiogenesis, has become an attractive approach for oncotherapy. However, classic anti-angiogenic agents have several limitations in clinical use, such as lack of specific targeting, low bioavailability, and poor therapeutic outcomes. Hence, alternative angiogenic inhibitors are highly desired. With the emergence of nanotechnology, various nanomaterials have been designed for anti-angiogenesis purposes, offering promising features like excellent targeting capabilities, reduced side effects, and enhanced therapeutic efficacy. In this review, we describe tumor vascular features, discuss current dilemma of traditional anti-angiogenic medicines in oncotherapy, and underline the potential of nanomaterials in tumor anti-angiogenic therapy. Moreover, we discuss the current challenges of anti-angiogenic cancer treatment. We expect that this summary of anti-angiogenic nanomaterials in oncotherapy will offer valuable insights, facilitating their extensive applications in the future.

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Background: Accumulating research substantiated that tumor-associated macrophages (TAMs) have a significant impact on the tumorigenesis, progression, and distant metastasis, representing a novel target for various cancers. However, the underlying dynamic changes and interactions between TAMs and tumor cells remain largely elusive in colorectal cancer (CRC). Methods: We depicted the dynamic changes of macrophages using sing-cell RNA-seq data and extracted TAM differentiation-related genes. Next, we utilized the weighted gene co-expression network analysis (WGCNA) to acquire CMS-related modular genes using bulk RNA-seq data. Finally, we utilized univariate Cox and Lasso Cox regression analyses to identify TAM differentiation-related biomarkers and established a novel risk signature model. We employed quantitative real-time polymerase chain reaction (qRT-PCR) on CRC tissue samples and used immunohistochemistry (IHC) data frome the HPA database to validate the mRNA and protein expression of prognostic genes. The interaction of TAMs and each consensus molecular subtype (CMS) subpopulation was analyzed at the cellular level. Results: A total of 47,285 cells from single-cell dataset and 1197 CRC patients from bulk dataset were obtained. Among those, 6400 myeloid cells were re-clustered and annotated. RNASE1, F13A1, DAPK1, CLEC10A, RPN2, REG4 and RGS19 were identified as prognostic genes and the risk signature model was established based on the above genes. The qRT-PCR analysis indicated that the expression of RNASE1 and DAPK1 were significantly up-regulated in CRC tumor tissues. The cell-cell communication analysis demonstrated complex interactions between TAMs and CMS malignant cell subpopulations. Conclusion: This study presents an in-depth dissection of the dynamic features of TAMs in the tumor microenvironment and provides promising therapeutic targets for CRC.

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Calcium (Ca2+) is essential for mitochondrial homeostasis and function coordination, particularly in cancer cells that metabolize frequently to sustain their growth. Photochemistry mediated calcium overload has attracted lots of attention as an effective way to achieve tumor suppression. Herein, we developed a photonanomedicine to synergistically induce calcium overload via cell-surface photochemistry and thus tumor suppression. Specifically, the photosensitizer, protoporphyrin IX (PpIX) was loaded onto upconversion nanoparticles (UCNP), which was subsequently modified by a polymer bearing photo-crosslinking cinnamate (CA) groups. The resulting nanoparticle was further functionalized by anti-CD20 aptamers (Apt), to give photonanomedicine. The interaction between CD20 receptors and anti-CD20 aptamers allowed photonanomedicine to accurately attach onto the Raji cell surface after an intravenous injection. Following the local application of a 980 nm NIR laser, the photonanomedicine was able to capture the NIR light and convert it into ultraviolet (UV) light. On one hand, the converted UV light led the crosslinking of cinnamate groups in photonanomedicine, further stimulating the clustering of CD20 receptors and causing Ca2+ influx. On the other hand, the UV light could simultaneously excited PpIX to generate reactive oxygen species (ROS) in situ to break down the integrity of cell membrane and lead to an influx of Ca2+. The synergistic Ca2+ overload mediated by photonanomedicine exhibited an enhanced and superior anti-tumor efficacy. We believe this photonanomedicine expands the toolbox to manipulate intracellular Ca2+ concentration and holds a great potential as an anti-tumor therapy.

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Antibodies represent a relatively mature detection means and serve as therapeutic drug carriers in the clinical diagnosis and treatment of cancer-among which monoclonal antibodies (mAbs) currently occupy a dominant position. However, the emergence and development of small-molecule monodomain antibodies are inevitable due to the many limitations of mAbs, such as their large size, complex structure, and sensitivity to extreme temperature, and tumor microenvironments. Thus, since first discovered in Chondroid fish in 1995, IgNAR has become an alternative therapeutic strategy through which to replace monoclonal antibodies, thus entailing that this novel type of immunoglobulin has received wide attention with respect to clinical diagnoses and tumor therapies. The variable new antigen receptor (VNAR) of IgNAR provides an advantage for the development of new antitumor drugs due to its small size, high stability, high affinity, as well as other structural and functional characteristics. In that respect, a better understanding of the unique characteristics and therapeutic potential of IgNAR/VNAR in clinical and anti-tumor treatment is needed. This article reviews the advantages of its unique biochemical conditions and molecular structure for clinical diagnoses and novel anti-tumor drugs. At the same time, the main advantages of the existing conjugated drugs, which are based on single-domain antibodies, are introduced here, thereby providing new ideas and methods for the development of clinical diagnoses and anti-tumor therapies in the future.

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BACKGROUND/AIM: To obtain sufficient numbers of high-quality natural killer (NK) cells, we developed feeder cells using synthetic biology techniques. MATERIALS AND METHODS: K562 cells were engineered to express membrane bound interleukin-2 (mbIL2) or interleukin-13 (mbIL13). RESULTS: The incubation of human primary NK cells isolated from peripheral blood mononuclear cells (PBMCs) with these feeder cells significantly increased the number of activated NK cells compared to K562 parental cells. Fluorescence-activated cell sorting (FACS) analysis demonstrated that NKG2D activating receptors were abundant on the surface of NK cells expanded by K562-mbIL2 or mbIL13 cells. NK cells expanded on K562-mbIL2 or mbIL13 lysed cancer cells more effectively than those cultured with normal K562 cells. Using NK cells incubated with our feeder cells, we developed anti-CD19 chimeric antigen receptor (CAR)-NK cells. They showed robust cytotoxic effect against CD19 positive cancer cell line. CONCLUSION: Our newly developed feeder cells could provide useful tools for NK cell therapy.

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