Cancer cells undergo profound metabolic reprogramming to support their uncontrolled proliferation and survival. Many studies have shown that arginine promotes tumor growth. In liver cancer cells, even when the expression of arginine synthesis genes is reduced, the cells can increase the amount of arginine to maintain tumor cell growth (1). Arginine deprivation directly leads to the death of cancer cells (2), so directly reducing the amount of arginine in tumor cells has become an important tumor treatment method, which is also known as arginine deprivation therapy (3).

The arginine metabolism axis intersects with multiple hallmarks of cancer. Intracellular arginine serves as a precursor for polyamine synthesis, supporting cancer cell growth (4, 5), and for nitric oxide (NO) production (6), influencing angiogenesis and signaling. Its depletion triggers integrated stress responses, disrupts mitochondrial function, and can induce cell cycle arrest and apoptosis specifically in ASS1-deficient tumor cells. However, resistance mechanisms, including adaptive re-expression of ASS1 (7), and the complex role of arginine in modulating the tumor immune microenvironment where it can either support T-cell function or be catabolized by myeloid-derived suppressor cells to promote immunosuppression (8), present both opportunities and challenges.

This review aims to synthesize current knowledge on the molecular mechanisms by which targeting arginine metabolism inhibits tumor progression. We provide a critical review and discussion of therapeutic strategies, from direct arginine depletion using pegylated arginine deiminase (ADI-PEG20) and recombinant human arginase to pharmacological inhibition of enzymes like arginase and nitric oxide synthase. Furthermore, we explore emerging combinatorial approaches that leverage arginine deprivation therapy to potentiate chemotherapy, radiotherapy, and immunotherapy, and ultimately discuss future directions for translating these metabolic insights into more effective and personalized anticancer regimens.

During infancy, growth periods, pregnancy, and illness, the body’s synthesis of arginine is insufficient to meet the cells’ demand for arginine, so dietary supplementation is needed; therefore, arginine is considered a semi-essential amino acid (9). Arginine can not only be interconverted with proline and glutamate, but also serves as a precursor for the synthesis of proteins, nitric oxide, creatine, polyamines, agmatine, and urea (10). The concentration of arginine is increased in various tumors and is a key amino acid for regulating and adapting the immune system. Its metabolic derivatives, such as NO and polyamines, participate in the occurrence and development of tumors (11). In the human body, arginine is primarily synthesized through the urea cycle (in the liver) and the cytoplasmic pathway in tissues such as the kidneys and intestines, with the kidneys being the main organ responsible for net arginine synthesis (12). Arginine metabolism occurs via multiple pathways. Arginine produces NO through the NOS pathway, regulating cardiovascular, neural, and immune functions (13); arginase catalyzes the conversion of arginine to ornithine, which is then used to synthesize polyamines and proline. Polyamines contribute to cell proliferation and repair, while proline is involved in collagen synthesis and tissue repair. Arginase I mainly detoxifies ammonia in the liver (14), whereas arginase II regulates polyamine/proline synthesis and immune balance in extrahepatic tissues (15); arginine-depleting enzymes can catalyze L-arginine to generate agmatine, which regulates neural and vascular relaxation (16); L-arginine:glycine amidinotransferase (GATM) catalyzes the transfer of a guanido group from arginine to glycine, forming guanidinoacetic acid, the immediate precursor of creatine (17); L-Arginine deiminase (ADI) catalyzes the hydrolysis of arginine to citrulline and ammonia. The main way the gut microbiota metabolizes arginine is through ADI (18).

Arginine, especially L-arginine, can regulate T cell metabolism, thereby improving T cell survival and their role in anti-tumor immunity. Studies have demonstrated through a series of experiments that active urea and citrulline cycles exist in CD8 memory T cells, which are crucial for enhancing T cell immune memory. It was found that CD8 T cells can synergistically clear ammonia through the urea and citrulline cycles, regulating the CPS1-ARG2 axis to enhance T cell memory and anti-tumor immune capacity (59). Researchers analyzed metabolic and proteomic changes in human primary CD4 T cells activated at different time points using liquid chromatography-mass spectrometry (LC-MS) and found that increasing L-arginine concentration can promote T cells to shift from glycolysis to oxidative phosphorylation (OXPHOS), improve mitochondrial function, enhance oxygen consumption and spare respiratory capacity, provide bioenergetic support for T cells, and thereby enhance their persistence and efficacy in antitumor immunity (60). Further studies have found that the effect of L-arginine on T cell survival is partially mediated through the regulation of nuclear proteins such as BAZ1B, PSIP1, and TSN (61). These proteins exhibit different conformational changes in the presence of L-arginine, and gene editing to delete these genes reduces T cells’ dependency on L-arginine, further supporting the crucial role of L-arginine in T cell survival (61) (Figure 2). Overall, L-arginine not only enhances T cell survival by promoting oxidative metabolism, but also improves their anti-tumor response by strengthening the memory phenotype of T cells. This finding provides a new strategy for cancer immunotherapy, particularly in the context of CAR T cell therapy and immune checkpoint inhibition, further exploring the potential of L-arginine as a metabolic regulator.

Arginine is needed for both the activity of immune cells, especially T cells, and the growth of cancer cells. Arginine deprivation therapy has shown anti-tumor potential in the treatment of tumors with ASS1 deficiency or low expression (62). Clinical studies on arginine deprivation have mainly focused on using recombinant arginine deiminase (such as ADI-PEG 20) as a treatment approach. ADI-PEG 20 can convert arginine into citrulline and ammonia, thereby reducing intracellular arginine levels in tumor cells (Figure 2). However, there are some challenges in the clinical application of ADI-PEG 20, such as the rapid upregulation of ASS1 in certain tumor cells, which limits the efficacy of arginine deprivation when used alone. In addition, factors such as ASS1 upregulation, autophagy, metabolic cooperation between the tumor stroma and tumor cells, as well as the production of resistance antibodies can affect the effectiveness of arginine deprivation therapy (63). To overcome these problems, researchers have proposed some possible solutions, such as combining arginine deprivation with chemotherapeutic drugs, or using non-immunogenic arginase. Other studies have shown that polyamine metabolism is altered in ASS1-deficient cells. In the absence of arginine, the levels of polyamines in these cells decrease, but polyamine biosynthetic enzymes are compensatorily upregulated. In ASS1-deficient cells, blocking polyamine synthesis with DFMO (an ODC1 inhibitor) significantly increases cell death, providing a therapeutic opportunity for targeting polyamine metabolism (64). The study results also indicate that levels of polyamines (such as putrescine) in plasma can serve as biomarkers to predict patients’ responses to ADI-PEG20. In addition, combining ADI-PEG20 with polyamine synthesis inhibitors (such as DFMO) may provide a synergistic therapeutic approach for ASS1-deficient cancers.

Many cancer cells rely on exogenous arginine for survival, so depleting exogenous arginine has become an effective anti-cancer strategy. Using modified recombinant human arginase [HuArgI (Co)-PEG5000] to remove arginine from the tumor microenvironment enables targeted treatment of pancreatic cancer cells. Research has also revealed that arginine deprivation induces autophagic cell death by activating the autophagy pathway (65). Other research results indicate that pancreatic cancer cells (Panc-1, Capan-1, Hs 766 T, Panc 04.03, and Panc 10.05) exhibit varying degrees of dependence on arginine, and arginine depletion induced by [HuArgI (Co)-PEG5000] can effectively kill these cells (66). There are also studies on the use of recombinant human arginase [HuArgI (Co)-PEG5000] to inhibit the growth of colon cancer cells by depleting arginine. These studies confirmed that arginine deprivation induced by [HuArgI (Co)-PEG5000] can effectively activate autophagy and lead to the death of colon cancer cells (67). This mechanism provides new ideas for the targeted therapy of pancreatic cancer and colon cancer. Under arginine deprivation conditions, in melanoma cells, c-Myc replaces HIF-1α in binding to the E-box in the AS promoter region, promoting the upregulation of AS expression, thereby reducing the therapeutic effect of ADI-based arginine deprivation (68).

Research has found that methylation of the ASS1 promoter is an important predictive marker for the sensitivity of lymphoma cells to arginine deprivation therapy. Treatment combining arginine deprivation with autophagy inhibitors may provide a new therapeutic strategy for lymphoma patients (69). Matthew Fletcher and others focused on studying how L-arginine (L-Arg) depletion suppresses T cell antitumor responses by inducing myeloid-derived suppressor cells (MDSCs), and explored the role of PEGylated arginase (peg-Arg I) therapy in the tumor immune environment (70). The study used mouse models and in vitro T cell culture models to investigate the effects of L-arginine depletion on T cell proliferation, metabolism, and survival. The results showed that treatment with peg-Arg I significantly inhibited the proliferation of activated T cells, but did not induce T cell apoptosis or affect the expression of activation markers such as CD25, CD69, and IL-2. It was also found that T cell glycolysis was markedly suppressed, while mitochondrial respiration remained unchanged, indicating that T cells maintain survival through enhanced oxidative metabolism (71). L-arginine deprivation therapy has a dual effect. While this method can effectively inhibit the growth of tumor cells that depend on L-arginine, it can also suppress the anti-tumor response of normal T cells by inducing the accumulation of MDSCs (Figure 2). Therefore, when treating cancer patients with peg-Arg I, it is necessary to combine it with strategies that inhibit MDSCs (72). Another study found that α-difluoromethylornithine (DFMO) can reduce the expression and activity of arginase (Arg1) in MDSCs by inhibiting ornithine decarboxylase (ODC) activity, and suppress the CD39/CD73-mediated adenosinergic pathway, thereby restoring T cell-mediated anti-tumor immune responses (73). Werner A and colleagues studied how activated T cells use citrate as a precursor to synthesize arginine, thereby overcoming the inhibition of T cell function caused by arginine deficiency. The researchers explored promoting T cell proliferation in an arginine-deficient environment through exogenous supplementation of citrate, which can be converted into arginine via enzymatic reactions, including the actions of argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) (74). Studies have found that when the concentration of exogenous arginine is 20 µM, supplementation with citrate can significantly restore T cell proliferation, whereas at arginine concentrations of 5 µM or 0 µM, citrate fails to restore T cell proliferation (74) (Figure 2). Research has also found that circulating L-arginine can predict the survival of cancer patients receiving immune checkpoint inhibitors (ICIs) therapy (75). Researchers found through the analysis of multiple ICI clinical trials that the level of L-arginine in patients’ blood can predict their response to ICI immunotherapy (76). This is mainly based on the fact that L-arginine metabolism is an important pathway for regulating immune cells, especially in controlling the activity of T cells. The potential mechanism may be that ICIs activate the immune system, increasing the synthesis and release of L-arginine by immune cells, including T cells, which in turn activates more immune cells, helping the patient survive.

Researchers analyzed the serum metabolite levels of 392 renal cancer patients and found that patients with higher L-arginine levels had significantly longer survival. Clinical trial data showed that patients with high blood ARG levels (ARG ≥42 mM) exhibited better clinical responses, including improved clinical benefit, progression-free survival (PFS), and overall survival (OS) (75). In a PD-1 inhibitor-sensitive MC38 colon cancer mouse model, experimental mice with high baseline ARG levels showed higher tumor rejection rates and longer survival.

Transfer RNA (tRNA) is a key molecule in decoding the genetic code during translation and is rich in numerous post-transcriptional modifications. Studies have found that arginine-to-cysteine substitutions (R>C substitutants) are significantly enriched in the lung cancer proteome. This enrichment is induced by arginine deprivation, potentially through tRNA misalignments, and is associated with mutations in the KEAP1 pathway. R>C substitutants enhance lung cancer cell resistance to cisplatin (88). Studies have also confirmed that colorectal cancer cells lacking arginine first reduce arginine transfer RNAs, after which ribosomes stall at arginine codons (89). Genes having mutations in arginine codons can help tumor cells overcome arginine deprivation. Therefore, arginine deprivation induces genomic mutations and proteomic changes in cancer cells (89).

Even under conditions of amino acid limitation, translation can be regulated through ribosome restriction. Amino acids can modulate protein synthesis in mammalian cells through a mechanism known as ‘ribosome pausing.’ Darnell and colleagues primarily studied the responses of the mTORC1 and GCN2 pathways to tRNA charging and ribosome stalling under conditions of arginine and leucine deficiency. Their findings showed that mTORC1 and GCN2 can relieve the loss of tRNA charging and ribosome stalling caused by leucine deprivation; however, these pathways were ineffective against the loss of tRNA charging and ribosome stalling induced by arginine deprivation (81) (Figure 4).

Arginyl-tRNA-protein transferase 1 (ATE1) primarily functions to transfer arginine to the N-terminal aspartate or glutamate residues of proteins, facilitating their degradation via the ubiquitin pathway. Abeywansha and colleagues conducted an in-depth study of the structure of ATE1 from Saccharomyces cerevisiae and its interaction with tRNA^Arg. ATE1 can perform the arginylation reaction through contacts between its GNAT fold domain and the groove of the tRNA acceptor stem, as well as the 3’-CCA end (90). Protein arginylation is catalyzed by the enzyme ATE1, which uses tRNA^Arg as the amino acid donor. Since the use of tRNA^Arg competes with protein synthesis, the specificity of ATE1 during translation becomes an important issue (Figure 4). Lan focused on the three-dimensional structure of human ATE1 in complex with its substrate (91). This provides a new perspective for understanding the complex regulatory mechanisms of protein arginylation, especially the interplay between translation and modification, and also reveals its potential as a therapeutic target in cancer.

METTL1 is an RNA methyltransferase of the METTL family that catalyzes m7G modification in tRNA and is involved in cell cycle regulation and the translation of cancer-related genes. Studies have found that METTL1 is overexpressed in various cancers and is associated with poor prognosis. It was revealed that METTL1 enhances mRNA translation efficiency by catalyzing m7G modification of tRNA (especially Arg-TCT-4-1), particularly increasing the translation efficiency of mRNAs for cell cycle regulators that are rich in AGA codons. Arg-TCT is upregulated in many cancer cells and promotes oncogenic transformation, providing a new target for precise cancer therapy (92).

One of the mechanisms of immune evasion in cancer is through immune checkpoint inhibition, particularly the interaction between PD-1 and PD-L1. PD-L1 is overexpressed on the surface of many types of cancer cells and tumor-infiltrating immune cells, helping tumor cells evade T cell immune surveillance and limiting the function of the immune system (93). In recent years, the clinical application of immune checkpoint inhibitors (such as pembrolizumab) has significantly changed the landscape of cancer treatment. However, the survival of tumor cells also involves other mechanisms, among which autophagy, as a cellular self-protection mechanism, plays a dual role in the growth and survival of tumor cells. Robainas M. and colleagues focused on exploring the interaction between the PD-1/PD-L1 pathway and autophagy in tumor immune evasion and therapy, finding that PD-L1 helps tumor cells survive under immune pressure by activating autophagy, especially in nutrient-deprived and hypoxic tumor microenvironments. The study also found that in multiple mouse tumor models, the combination of immune checkpoint inhibitors and autophagy inhibitors exhibited significant antitumor activity (94).

Arginine deficiency in the tumor microenvironment can weaken the expression of CTLA4 and PD-1 on activated T cells, thereby inhibiting the proliferation of activated T cells (95). Supplementing arginine in vitro is also considered a potentially valuable anti-tumor therapeutic strategy, but arginine supplementation carries the risk of promoting tumor cell proliferation. Specifically increasing the concentration of arginine within T cells may potentially address this issue. For example, stably expressing ASS1 and OTC in T cells and cooperating with different chimeric antigen receptors (CARs) can enable the recycling of ornithine into arginine, thereby enhancing the antitumor function and survival of CAR-T cells (96).

Given the complexity of arginine requirements among different immune cells in tumor cells and the tumor microenvironment, specifically targeting the arginine transport process on cells is a feasible strategy (97). The arginine transporter SLC7A1 is involved in the progression of hepatoblastoma and ovarian cancer (98). The expression of the SLC7A2 gene has been identified as an independent prognostic biomarker for breast cancer (99), and its low expression enhances multidrug resistance in non-small cell lung cancer (NSCLC) (100), reduces immune infiltration, and leads to poor prognosis (101). Related studies have indicated that SLC7A3 is a prognostic biomarker for breast cancer (102). These pieces of evidence collectively suggest that targeting arginine transport to block tumor cells from utilizing exogenous arginine is a potentially effective antitumor strategy.

Research by Cook and colleagues demonstrated that immunization with citrullinated ENO1 peptide segments can induce a strong Th1 response. Citrullinated ENO1 peptide segments can be used to treat melanoma, pancreatic cancer, and lung cancer. The study results indicate that citrullinated antigens can effectively activate the immune system and enhance anti-tumor immune responses, particularly when tumor cells undergo stress responses such as nutrient deprivation. The study also shows that citrullinated ENO1 is effective not only under specific HLA types but also in individuals with different HLA types, making it a candidate vaccine with broad clinical application potential (103).

ADI-PEG 20 (PEGylated arginine deiminase) is an enzyme that depletes arginine by converting it into citrulline and ammonia (104) (Figure 5). It is currently used for malignant pleural mesothelioma, hepatocellular carcinoma (for which Phase III clinical trials have been conducted), melanoma, non-small cell lung cancer (NSCLC), acute myeloid leukemia (AML), and uveal melanoma (105). This enzyme achieved longer PFS (106) and other clinical outcomes in Phase I and II clinical trials (107). Brin E. focused on studying the role of ADI-PEG 20 in the tumor immune microenvironment and found that ADI-PEG 20 not only regulates immune checkpoints by affecting PD-L1 expression on tumor cells, but also improves the tumor immune microenvironment by reducing Treg cell accumulation and promoting T cell infiltration (108). This provides a new perspective for future cancer immunotherapy, especially in tumor types that exhibit immune evasion, where ADI-PEG 20 may become an effective immunomodulator.

In addition, a modified human arginase-1 (pegzilarginase) that can deplete systemic arginine shows significantly better tumor growth control when combined with immunotherapy drugs such as anti-PD-L1 or agonist anti-OX40 than with monotherapy (109). It also enhances the activity of CD8 T cells, aiding immune-mediated tumor clearance. This new finding provides a promising strategy for treating cancers that depend on exogenous arginine and for improving the efficacy of immunotherapy. The combination of pegzilarginase and immunotherapy enhances antitumor immune responses by increasing CD8 T cells and promoting the polarization of tumor-associated macrophages toward the M1 type. BCT-100 (Pegylated Recombinant Human Arginase 1) is a recombinant human arginase 1 that, after PEGylation, reduces immunogenicity and prolongs its half-life. It depletes arginine by hydrolyzing it into ornithine and urea, thereby exerting an antitumor effect (Figure 5). Currently mainly used to explore treatments for hepatocellular carcinoma (HCC) (110) and melanoma (111). In vitro and mouse models showed that BCT-100 can significantly reduce arginine levels in bladder cancer, inhibit the AKT/mTOR pathway, induce autophagy and apoptosis, and suppress tumor growth (112).

Research by Cao Y. and colleagues using a 4T1 breast cancer mouse model showed that both L-arginine and docetaxel (DTX) alone could significantly inhibit tumor growth, while the combination of L-arginine and docetaxel exhibited the strongest tumor-suppressing effect. The combined treatment of DTX and L-Arg was able to significantly enhance the anti-tumor immune response in mice, increase immune cell infiltration in the tumor microenvironment—particularly dendritic cells and effector T cells—and reduce the proliferation of MDSCs (113). This study provides a new potential strategy for the treatment of breast cancer. By combining L-arginine and docetaxel, it not only directly inhibits tumor growth but also activates anti-tumor immune responses by modulating the immune system.

The arginase inhibitor CB-1158 (INCB001158) selectively inhibits arginase activity (mainly Arg1) in the tumor microenvironment, increases arginine levels in the TME, and enhances the activity of tumor-infiltrating CD8 T cells and NK cells, thereby improving anti-tumor effects (114) (Figure 5). It is currently applicable to various solid tumors, including colorectal cancer (MSS CRC), NSCLC, and melanoma, and is often used in combination with PD-1/PD-L1 inhibitors. The combination therapy of Retifanlimab and CB-1158 has a relatively high safety profile (115). Nor-NOHA is a small molecule arginase inhibitor, primarily studied in vitro or in animal models to investigate the effects of ARG inhibition on tumor or immune cells (116). To cope with the effects caused by ADI-PEG20, tumor cells initiate the autophagy process to replenish arginine deficiency, thereby allowing tumor cells to survive. Therefore, the combined use of ADI-PEG20 and the autophagy inhibitor chloroquine can effectively suppress tumor growth (117).

Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous malignancy that is often associated with poor prognosis. PTCL cells rely on the arginine transporter SLC3A2 for the uptake of exogenous arginine, which in turn supports tumor cell proliferation and immune evasion. Research found that SSRP1 acts as a transcriptional co-activator and, together with JUNB, regulates the transcription of SLC3A2. Quinacrine inhibits the transcription and expression of SLC3A2 by targeting SSRP1, thereby reducing intracellular arginine levels, suppressing PTCL cell proliferation, and inducing apoptosis. Therefore, quinacrine and histone deacetylase inhibitors are considered effective therapeutic candidate drugs (118).

The GCN2-eIF2α-ATF4 pathway has been identified as the classical pathway responding to amino acid deficiency (119). Recently, through high-throughput screening, Chen et al. discovered that BAG2 acts as an arginine-sensing protein, and its glutamine residue 167 binds to arginine. The study revealed that when arginine is abundant, BAG2 binds to SAMD4B, inhibiting β-catenin degradation and promoting cell proliferation; when arginine is deficient, BAG2 releases SAMD4B, which then binds to β-catenin and promotes its degradation, thereby enhancing ATF4 stability and supporting cell survival. Further research found that the BAG2-SAMD4B pathway works in concert with the classical GCN2-eIF2α-ATF4 pathway to collectively regulate the stress response, helping tumor cells cope with the stress caused by arginine deprivation (120). This study provides a new approach, suggesting that treatment with arginine deprivation combined with an ATF4 inhibitor (such as ATF4-IN-1) may effectively suppress tumor cell growth.

The tumor microenvironment (TME) is a tissue composed of tumor cells, immune cells, and other cells and molecules, characterized primarily by immunosuppression and metabolic reprogramming. Scientists from the Chinese Academy of Sciences have revealed a novel mechanism in which breast cancer cells lead to pro-tumor polarization of tumor-associated macrophages (TAMs) through providing arginine, thereby helping tumor cells evade immune attacks (5). Mechanistically, polyamines produced from arginine metabolism enhance pro-tumor TAM polarization through DNA demethylation mediated by thymine DNA glycosylase (TDG), while the interaction between breast cancer cells and TAMs diminishes the ability of arginine to increase CD8 T cell activity. Targeting the arginine-polyamine-TDG axis can effectively inhibit breast cancer cell growth.

In 2013, it was discovered that BCT-100, after PEGylation, can hydrolyze arginine into ornithine and urea; In 2016, it was found that in ASS1-deficient tumors, arginine depletion induces nutrient starvation through ADI-PEG20, chloroquine inhibits autophagy, and the combination of the two can enhance cell death; In 2017, CB-1158 was found to selectively inhibit arginase activity (mainly Arg1) in the tumor microenvironment, and thereby improving anti-tumor effects; In 2017, a new drug PBT (composed of DFMO and Trimer PTI) was found to inhibit polyamine metabolism, significantly suppressing tumor growth;In 2017, it was discovered that ADI-PEG 20, after PEG modification, can deplete arginine in the tumor microenvironment; In 2019, Human recombinant arginase I (Co)-PEG5000 [HuArgI (Co)-PEG5000] could effectively activate autophagy and lead to colon cancer cell death; In 2020, Nor-NOHA was identified as a small molecule arginase inhibitor; In 2021, pegzilarginase was used in combination with immunotherapy drugs such as anti-PD-L1 or anti-OX40; In 2024, Indisulam has been found to inhibit liver cancer cells by degrading RBM39 through the E3 ubiquitin ligase-proteasome pathway; In 2025, it was discovered that intervening in the BAG2-SAMD4B pathway could potentially enhance the effects of tumor arginine deprivation therapy; In 2025, it was discovered that quinacrine inhibits the transcription and expression of SLC3A2 by targeting SSRP1, thereby reducing intracellular arginine levels, inhibiting PTCL cell proliferation and inducing apoptosis.

Arginine is a nutrient required for the development and survival of various tumors. Naturally, depleting arginine within tumor cells has become one of the methods for treating tumors. In oncology, this method is referred to as arginine deprivation therapy (121). However, arginine deprivation therapy faces inherent bottlenecks, such as weakening the function of immune cells in the body. We discussed in detail how to use arginine deprivation therapy while enhancing the body’s immune function, especially the activity of T cells.

With the elucidation of the molecular mechanisms of arginine metabolism and the molecular mechanisms that maintain high intracellular levels of arginine in cancer cells, our review not only summarizes the application and molecular mechanisms of arginine deprivation therapy in tumors (122), but also reviews and discusses the synthesis and modification of tRNA-Arg, which are gradually becoming hot targets in cancer treatment. At the same time, effector proteins from microorganisms and metabolites from plants (123), together with arginine deprivation therapy, have become effective means of killing tumor cells (124). The molecular mechanisms and applications of arginine deprivation therapy and other therapies, such as immunotherapy, are also well discussed and analyzed in this article.

Our research has more thoroughly advanced arginine deprivation therapy from both molecular mechanisms and applications. Our review can better provide methods and guidance for clinicians in treating cancers caused by arginine metabolism disorders.