The VEGF signaling pathway consists of various VEGF ligands and receptors, including VEGF-A, B, C, D, E, F, and placental growth factor, along with receptors such as VEGFR1, 2, and 3. VEGF-A acts as the primary agent that triggers the activation of endothelial cells (ECs) for angiogenesis (6). It attaches to VEGFR2 located on the ECs’ surface, resulting in the phosphorylation of its intracellular domain and the ensuing activation of downstream signaling cascades, including PI3K/AKT and MAPK/ERK. These mechanisms promote the proliferation and migration of ECs, thereby aiding in neovascularization. As a result, VEGF-A has become a significant focus for anti-angiogenic treatments. Additionally, VEGF is an essential factor in angiogenesis that drives the creation of disorganized and primitive blood vessels in various tumor tissues. It initiates various biological processes, many of which are linked to cancer (7); therefore, VEGF has turned into a critical target for anti-angiogenic therapies.

The FGFR family encompasses FGFR1 to FGFR5, characterized by a sequence that is notably conserved and homologous. Comprising an extracellular domain, a hydrophobic transmembrane domain, and an intracellular domain responsible for tyrosine kinase activity, FGFR1 to FGFR4 exhibit considerable conservation across these receptors. Conversely, FGFR5 does not possess the intracellular tyrosine kinase domain, leading to its overactivity in the regulatory fibroblast growth factor (FGF) - FGFR signaling pathway (8, 9). The fibroblast growth factor receptor (FGFR) is classified as a receptor tyrosine kinase (RPTK). The activation of the FGFR signaling axis primarily relies on the binding of the ligand FGF to the FGFR dimer, followed by dimerization with fibroblast growth factor receptor substrate 2 (FRS2) and subsequent autophosphorylation. The activation of downstream signaling pathways, including PI3K/AKT and RAS-MAPK, is initiated by this cascade, both of which are crucial for regulating cell proliferation and apoptosis (10, 11).

Platelet-derived growth factor (PDGF) represents an important category of growth factors, predominantly secreted by platelets, and is essential in the mechanisms of cell proliferation, migration, and differentiation (12). This factor typically exists as a homodimer, primarily consisting of PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC, and PDGF-DD. It exerts its effects through specific receptors, namely PDGFR-α and PDGFR-β. The binding of PDGF to these receptors activates intracellular signaling pathways, including the PI3K/Akt and MAPK pathways, which promote cell proliferation, migration, lumen formation, and the development of new blood vessels (13, 14). PDGF exhibits a dual role in tumor development; it not only supports tumor growth by enhancing the proliferation and migration of tumor-associated fibroblasts but also promotes tumor angiogenesis, thereby increasing the nutrient supply to tumors (15).

Transforming growth factor alpha (TGF-α) is a small, varied factor belonging to the epidermal growth factor (EGF) family. It plays an essential role in controlling cell growth, differentiation, migration, and survival (16). The effects of TGF-α are mediated through its interaction with the epidermal growth factor receptor (EGFR).This binding activates EGFR, resulting in dimerization and autophosphorylation of the receptor, which subsequently triggers downstream signaling pathways (17). Specifically, it activates the Ras/MAPK signaling pathway to promote cell proliferation and survival, as well as the PI3P/Akt pathway to enhance cell survival and inhibit apoptosis (18). Additionally, TGF-α can alter the tumor microenvironment, promoting vasculogenesis and metastasis (19).

The gC1qR protein, referred to as P32/C1qBP/HABP1, is a versatile protein that is found at elevated levels in various types of cancer and possesses prognostic significance. It governs multiple related signaling pathways, such as the Wnt/β-catenin, PKC-NF-κB, and Akt/PKB pathways, which may contribute to the promotion of apoptosis in tumor cells and possess antiangiogenic properties (81). In studies conducted by Peerschke E (82), both in vitro and in vivo experiments demonstrated that the specific monoclonal antibody gC1qR mAb 60.11 could inhibit tumor growth in mouse models of mesothelioma, consequently reducing the proliferation and spread of cancer cells, thus positioning it as a novel target for treating mesothelioma. Currently, several preclinical studies exploring gC1qR-targeted interventions, which include approaches like monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, and tumor vaccination, are being systematically pursued, yielding promising preclinical therapeutic outcomes (83). The investigation into the targeting of gC1qR marks an emerging area in cancer immunotherapy, offering both prospects and challenges for the progression of clinical treatments.

Platelet-derived growth factor (PDGF) represents a class of inhibitors that target PDGF and its receptors (PDGFR). PDGF binds to its receptor (PDGFR), initiating the cell signal transduction pathway and promoting angiogenesis and tumor cell proliferation (84). For instance, Imatinib was initially utilized as a therapeutic agent for acute myeloid leukemia and chronic myeloid leukemia, with its mechanism of action involving the inhibition of PDGFR, thereby demonstrating antitumor activity against certain solid tumors. Moreover, multitargeted tyrosine kinase inhibitors like Sunitinib and Sorafenib not only inhibit the vascular endothelial growth factor receptor (VEGFR) but also target PDGFR, demonstrating their efficacy in treating renal cell carcinoma (85) and hepatocellular carcinoma (86). Novel small-molecule targeted drugs have also entered preclinical or clinical trials, aiming to more precisely inhibit the PDGF/PDGFR signaling pathway without affecting other critical growth factor signaling pathways, thus attracting the attention of developers. Despite some advancements in the development of antitumor drugs targeting PDGF, challenges persist. For example, certain tumors have developed resistance to PDGF intervention (87, 88). Moreover, the specific roles and mechanisms of PDGF in various cancers, beyond lung and kidney cancers, require further elucidation.

Metalloproteinases (MMPs) are essential in the processes of angiogenesis and the spread of tumors. In the past few years, there have been notable improvements in the study of inhibitors for metalloproteases (89). Early MMP inhibitors, such as Marimastat, demonstrated some efficacy in preclinical and certain clinical trials; however, their widespread use has been limited due to side effects and efficacy concerns (90). The new generation of small-molecule MMP inhibitors aims to optimize selectivity and pharmacokinetic properties, with examples including Siramesin, BMS-981016, and BMS-845145. These novel compounds exhibit enhanced drug resistance and anti-tumor activity across various cancer types (91). Additionally, inhibitors targeting specific MMPs are under development, such as selective inhibitors against MMP-9, which may offer greater effectiveness and reduced side effects (92). While the prospects for new MMP targets are promising, challenges such as drug resistance and side effects persist. Consequently, enhancing the selectivity and relevance of these inhibitors remains a primary focus of current research and development.

Certain microRNAs (miRNAs) can regulate the expression of angiogenesis-related genes by binding to target mRNA, and current drugs targeting miRNAs are under development. miRNA replacement therapy involves introducing a tumor-suppressor miRNA that has been deleted or impaired, such as targeting the deleted miRNAs like miR-34a and miR-29. This area of research is actively progressing (93). MRX 34 is a nanoparticle medication derived from human miR-34a, specifically formulated for the treatment of liver cancer and is presently undergoing assessment for its safety and effectiveness in clinical trials (94). TargomiRs represent an endogenous miRNA repair therapy that utilizes liposome delivery systems encapsulating miRNA combined with targeting mechanisms (such as antibodies) to specifically target tumor cells and enhance the expression of tumor-suppressor miRNAs (95). AntagomiRs, developed in the form of antisense RNA, function by inhibiting specific tumor-promoting miRNAs (e.g., miR-21) (96). Ongoing studies on miR-155 inhibitors are also anticipated to facilitate treatment for lymphoma and some sarcomas (97). Novel tumor drugs based on miRNAs offer new hope for cancer treatment (93, 98, 99). However, despite their considerable potential, miRNA drugs face several challenges. For instance, the effective delivery of miRNAs or their inhibitors is a critical issue due to the biocompatibility and tissue specificity of the drugs themselves. Additionally, the specificity and durability of these drugs require attention to ensure the development of selective miRNA therapies that avoid potential adverse effects on normal cells, while also ensuring the stability and longevity of the drug within the body to prevent early degradation (100).

Antibody-drug conjugates (ADCs) combine antibodies with cytotoxic drugs to deliver toxins directly to the tumor microenvironment through targeted mechanisms, thereby reducing side effects (114, 115). The formation of new carrier proteins and the targeting of drugs to the tumor microenvironment can effectively enhance tumor distribution or activation, thus improving the anti-cancer activity against difficult-to-treat tumors (116). ADC molecules combine the accuracy of antibody-targeted tumor antigen recognition with powerful cytotoxic components, leading to targeted delivery systems for cancers. A key benefit of ADCs is their capacity to enhance the therapeutic index by precisely directing the cytotoxic payload to tumor tissues, which in turn lowers the minimum effective dose (MED) and notably reduces the incidence of adverse events (117). See Table 2 for details.

Peptide-drug conjugates (PDCs) represent an emerging class of targeted therapies composed of a carrier peptide, a toxic payload, and an adaptor that links the payload to the peptide. These conjugates demonstrate enhanced tumor permeability and increased specificity for targeted cancers (132). The first PDC approved by the FDA is Lu-177 DOTA-TATE (Lutatera), which is a conjugate of a radionuclide and the peptide octreotide. Singh S (133) and other studies have shown that the first-line treatment of 177Lu-Dotatate in combination with octreotide LAR significantly prolongs the median progression-free survival of patients with grade 2 or grade 3 advanced gastroenteropancreatic neuroendocrine tumors.For instance, Melphalan flufenamide(a first-in-class alkylating peptide-drug conjugate), In an open-label, phase III LIGHTHOUSE studyp (134)Shows, it has a good efficacy and a high safety profile in the treatment of triple-class refractory relapsed/refractory multiple myeloma (RRMM).ANG1005 is a brain-penetrating peptide-drug conjugate that consists of three paclitaxel molecules covalently linked to Angiopep-2. Research by Kumthekar P (135) and others indicates that ANG1005 exhibits high activity in breast cancer patients with leptomeningeal carcinoma and recurrent brain metastases.

Bispecific antibodies (BISpecific Antibodies) are a class of antibodies capable of simultaneously binding to two distinct target antigens. These antibodies can recognize and attach to two different molecules, typically targeting tumor surface antigens and the surfaces of immune cells. See Table 3 for details.

Other novel targeting antibodies, such as T-cell engager antibodies (TEGEV), are designed to direct T cells to tumors, thereby enhancing the immune system’s attack on cancer. Bispecific T-cell adapter (BiTE) therapy has emerged as one of the most promising treatments (147). For instance, Blinatumomab, an exemplary medication in BiTE therapy, has shown considerable effectiveness in treating advanced acute lymphoblastic leukemia (148). Furthermore, Tarlatamab (AMG 757), a molecule that conjugates dual-specific T cells and interacts with DLL3 and CD3, enhances tumor lysis mediated by T cells and has demonstrated promising outcomes in treating small cell lung cancer (149). Despite the advancements from traditional monoclonal antibodies to the next generation of antibody drugs, several challenges remain. First, drug resistance poses a significant obstacle; thus, developing therapies that address resistance mechanisms is a critical direction for future research. Second, the side effects of antibody drugs, particularly immune-related adverse reactions, require careful attention. The development of more selective antibodies aimed at minimizing these adverse reactions is also a key area of ongoing research.

Emerging anti-tumor treatment strategies such as Antibody-drug conjugates (ADCs), Peptide-drug conjugates (PDCs) and Bispecific antibodies (BsAb) not only have their own characteristics in mechanism, also show good therapeutic effects in clinical application, and gradually show their unique advantages and broad application prospects. However, it is worth noting that monotherapy is often difficult to meet the treatment needs of complex tumor microenvironment and specific tumors, and therefore, the combined application of drugs has gradually become an important research direction. Next, we will explore the strategies for combining antiangiogenic agents with other drugs and their potential advantages in cancer treatment.

Studies have demonstrated that the combination of Bevacizumab with chemotherapy agents, such as cisplatin and paclitaxel, can enhance therapeutic efficacy, particularly in non-small cell lung cancer, colorectal cancer, breast cancer, and other malignancies (150–154). The anti-VEGF antibody has been shown to increase tumor sensitivity to radiotherapy, and its combination with radiotherapy has yielded improved outcomes in liver cancer and brain tumors. Wang et al. (155) tracked 100 patients with esophageal cancer and found that the combination of Bevacizumab with gemcitabine and cisplatin resulted in significant clinical efficacy, effectively improving patient survival rates. Wilke et al. (156) conducted a randomized, placebo-controlled, double-blind phase 3 trial across North America, South America, and 170 countries in Europe, Asia, and Australia. After two years of clinical follow-up, they observed that the combination of paclitaxel and Bevacizumab for advanced gastric cancer outperformed the placebo and paclitaxel group. Additionally, Pfisterer et al. (157) explored the use of Bevacizumab in conjunction with platinum-based agents for recurrent ovarian cancer and established that the combination of carboplatin-PEGylated liposomal doxorubicin and Bevacizumab signifies a novel standard treatment choice for patients with platinum-eligible recurrent ovarian cancer. Eskander and colleagues (158) showed in a randomized phase 3 trial that was both double-blind and placebo-controlled that incorporating Pabolizumab into the standard chemotherapy regimen notably extended progression-free survival among patients suffering from advanced or recurrent endometrial cancer, in comparison to chemotherapy without the addition of Pabolizumab. Furthermore, after five years of clinical observation, de Castro Jr. et al. (159) discovered that patients with locally advanced or metastatic non-small cell lung cancer experienced enhanced treatment outcomes when treated with a combination of Pabolizumab and chemotherapy.

Tyrosine kinase inhibitors (TKIs), such as Sorafenib and Sunitinib, when combined with vascular endothelial growth factor (VEGF) inhibitors, can target multiple receptors and inhibit the proliferation and angiogenesis of tumor cells, resulting in a synergistic effect. In a single-arm phase II study, McNamara et al. (160) revealed that Axitinib showed promising and tolerable clinical efficacy in individuals with hepatocellular carcinoma (HCC) who had previously received VEGF inhibitors during the advanced stages of their illness. In the phase 3 COSMIC-312 study, Cabozantinib combined with Atezolizumab significantly improved progression-free survival compared to Sorafenib, showing enhanced disease control and reduced primary progression (161). Motzer and colleagues (162) discovered that the combination of Avelumab (a PD-L1 inhibitor) with Axitinib significantly extended progression-free survival and resulted in an objective response as the first-line treatment for advanced renal cell carcinoma. In an open-label phase 3 trial (KEYNOTE-426), Pembrolizumab combined with Axitinib significantly extended overall survival and progression-free survival, while also increasing objective response rates in previously untreated patients with advanced renal cell carcinoma (163). Long-term follow-up data revealed that the combination of Navolimab and Cabozantinib significantly enhanced overall survival in individuals suffering from advanced renal cell carcinoma, showcasing notable targeting and antitumor effects, with a median overall survival of 32.9 months (164). Xia et al. (165) concluded from a phase II clinical trial that perioperative Carilizumab combined with Apatinib showed promising efficacy and manageable toxicity in patients with resectable liver cancer. The phase 3 trial (CARES-310) conducted by Qin et al. (166) across 95 centers in 13 countries confirmed that Carilizumab provided statistically and clinically significant benefits in progression-free survival and overall survival, establishing it as a new effective first-line treatment option for this patient population. A phase Ib/IIa study showed that (167), allotinib (a multi-target TKI enzyme inhibitor) combined with natuluzumab (immune checkpoint inhibitor) showed a controlled safety and promising efficacy signal in the clinical treatment of non-small cell lung cancer (NSCLC). A phase Ib study (168) showed that vorolanib (a multi-target TKI inhibitor) and pembrolizumab or nivolumab (immune checkpoint inhibitor) showed lower toxicity and promising efficacy in the clinical treatment of advanced solid tumors.

Multi-target anti-angiogenic drugs, such as Cabozantinib, target VEGFR, MET, and other pathways, and their combination with immunotherapy, such as PD-1 antibodies, can significantly enhance anti-tumor efficacy. The preliminary interim evaluation of the randomized phase 3 KEYNOTE-811 study indicated that pabolizumab was evaluated in conjunction with trastuzumab, along with fluoropyrimidine and platinum-based chemotherapy, for individuals with HER2-positive metastatic gastric and gastroesophageal junction cancer, as opposed to a placebo. This interim analysis further demonstrated that the first-line combination of pabolizumab with trastuzumab and chemotherapy was superior to placebo in terms of progression-free survival (169). Margetuximab, an innovative Fc-engineered monoclonal antibody targeting HER2, boosts antibody-dependent cytotoxicity and may promote interaction between innate and adaptive immune systems. This effect is further intensified through checkpoint inhibition, leading to enhanced antitumor responses. Catenacci et al. first reported the combination of anti-HER2 and anti-PD-1 therapies in treating gastroesophageal adenocarcinoma, confirming the safety and efficacy of this approach through phase 3 of KEYNOTE-811 and phase 2 studies of INTEGA (170). Additionally, Shah et al. (171) utilized penpulimab and anlotinib in combination with albumin-bound paclitaxel/gemcitabine (PAAG) in patients with first-line metastatic pancreatic cancer, demonstrating the promising clinical efficacy of anti-angiogenic therapy combined with chemotherapy in this patient population. Conforti et al. (172) discussed the effectiveness and safety of using avelumab, an anti-PD-L1 inhibitor, in conjunction with the anti-angiogenic drug acacitinib for individuals suffering from advanced B3 thymoma and thymic carcinoma.

The combination of anti-angiogenic drugs and chemotherapy agents utilizing nanotechnology (such as liposomes and polymer nanoparticles) can enhance drug bioavailability and targeting, reduce side effects, and improve anti-tumor efficacy (173). See Table 4 for details.

Cell therapy, a form of immunotherapy, utilizes living cells as therapeutic agents to repair, replace, or enhance cellular function, thereby exerting a therapeutic effect. This category includes CAR-T cell therapy, T-cell immunotherapy, and cancer vaccines (181). CAR-T cell therapy involves the modification of a patient’s own T cells through genetic engineering to specifically identify and attack tumor cells. FDA-approved products such as Kymriah and Yescarta have demonstrated significant efficacy in treating acute lymphoblastic leukemia and large B-cell lymphoma, respectively (182). T-cell immunotherapy (183) enhances T cells by introducing them in vitro to the patient, employing technologies such as CRISPR/Cas9 (184) for optimization. Cancer vaccines are formulated using tumor cells or tumor-associated antigens, aimed at activating the body’s immune system to combat tumors. The combination of traditional anti-angiogenic drugs with emerging anti-tumor therapies can produce a synergistic effect, thereby enhancing overall efficacy. Combining anti-angiogenic drugs and cell therapy can improve the therapeutic effect on the one hand. The first use of anti-angiogenic drugs can improve the infiltration of immune cells (such as T cells, NK cells, etc.) in the tumor, and improve the effect of cell therapy. At the same time, antiangiogenic drugs can change the tumor microenvironment, reduce the immune escape ability of tumor cells, and promote the activity of T cells in cell therapy. On the other hand, by reducing drug resistance. The combination of these two treatments can inhibit adaptive changes in tumor cells, slow down drug resistance, and improve efficacy. Finally, the combination may allow lowering the dose required for cell therapy but maintain efficacy (185). At present, several clinical trials are evaluating the effect of combining antiangiogenic drugs with cell therapy, mainly in solid tumors such as mamomas, lung cancer, as well as some hematologic malignancies (such as leukemia, lymphoma), and have achieved good results. Zhang J and colleagues (186) engineered gene-specific targeted CAR-T cells using non-viral approaches via CRISPR-Cas9 technology. Their research indicated that employing non-viral anti-CD19 CAR-T cells integrated with PD1 resulted in an improved safety profile for patients suffering from relapsed or refractory invasive B-cell non-Hodgkin lymphoma (r/rB-NHL), characterized by a reduced rate of mild cytokine release syndrome (CRS) and the absence of neurotoxic effects. Elpamotide functions as an epitope peptide associated with the vascular endothelial growth factor receptor 2 (VEGFR-2), stimulating cytotoxic T lymphocytes (CTL) to target and eliminate VEGFR2-expressing endothelial cells. A single-arm phase II trial showed that gemcitabine with an antiangiogenic vaccine had good resistance and moderate antitumor effects in patients with advanced or recurrent biliary tract cancer (187).Wang and colleagues developed a ferritin nanoparticle platform modified with SpyCatcher that facilitates straightforward and stable covalent attachment to tumor-specific antigens containing SpyTag. They validated through experiments that ferritin nanoparticles loaded with either the HPV16 oncogene E7 peptide antigen or neoantigens derived from MC38 tumor mutations provoke a more robust antigen-specific cytotoxic T lymphocyte (CTL) response and significantly reduce the growth of tumors associated with E7 or MC38. Additionally, the therapeutic impact was further amplified when paired with a PD-1 checkpoint inhibitor (188) Figure 2 .

Antiangiogenic agents have been utilized in conjunction with oncolytic cells to enhance the anti-tumor effect (189, 190). These agents reduce tumor blood flow, thereby improving the infection efficiency of the oncolytic virus (191). A lower blood flow rate allows the oncolytic virus to remain within the tumor for a longer duration, facilitating its function. Additionally, antiangiogenic agents may decrease the immunosuppressive environment within the tumor, promoting more efficient replication of the oncolytic virus and its spread to adjacent tumor cells (192). Furthermore, these agents can inhibit tumor recurrence. To some extent, antiangiogenic drugs reduce immunosuppressive factors in the tumor microenvironment, thereby supporting the immune response triggered by oncolytic viruses and aiding in the prevention of tumor recurrence and metastasis (193). Concurrently, the combination of antiangiogenic drugs with oncolytic cells can enhance the immune response (194). The application of oncolytic cells induces the release and presentation of tumor antigens. In this context, antiangiogenic drugs can further opsonize the tumor microenvironment, thereby promoting the immune system’s response and anticancer activity (195). In recent years, several clinical trials have assessed the combination of anti-angiogenic drugs and oncolytic viruses, demonstrating promising efficacy in various refractory solid tumors, including pancreatic and liver cancers (196, 197). Endostatin, an angiogenesis inhibitor, plays a crucial role in tumor growth, tissue invasion, and metastasis. Some researchers have employed adenoviruses containing the human endostatin gene for intratumoral injection without any reported safety concerns. During treatment, serum levels of endostatin increased, and patients exhibited good tolerance (198). Oncolytic virus (OV) therapy represents a novel approach to cancer treatment. Chesney et al. conducted the first randomized trial evaluating the combination of T-VEC and ipilimumab for melanoma, which assessed the addition of oncolytic viruses to checkpoint inhibitors. The results indicated that the combination of Talimogene Laherparepvec and ipilimumab exhibited significantly higher efficacy compared to ipilimumab alone. This combination therapy demonstrated enhanced antitumor activity without introducing any additional safety concerns (199). Meng Y (200) constructed a novel dual-gene recombinant oncolytic adenovirus called RCAd-LTH-shPD-L1 based on the RCAd virus platform, emphasizing the potential of combining local virotherapy and antiangiogenic therapy with ICIs as an effective TME therapy for the treatment of poorly infiltrating tumors. Additionally, the MASTERKEY-265 trial, a Phase Ib/III investigation, assessed the effectiveness of T-VEC in combination with pembrolizumab for individuals with unresectable stage IIIB-IVM1c melanoma. The study demonstrated enhanced antitumor activity and verified that there were no unidentified safety concerns (201).

The initial strategy emphasizes vascular endothelial growth factor (VEGF) along with its receptors. One can evaluate the expression levels of VEGF or its receptors through immunohistochemistry (IHC) (202, 203) or molecular biology assays (204). In tumors, heightened levels of VEGF or its receptors often indicate a likelihood of responding to anti-VEGF therapies (205). The second approach examines the characteristics of the tumor microenvironment. Elevated levels of inflammatory markers, such as T cells, in certain tumors may suggest a greater responsiveness to anti-angiogenic drugs (206). The third approach is based on molecular markers. Mutations in specific oncogenes (e.g., HRAS, KRAS) (207) may be associated with sensitivity to anti-angiogenic therapies, necessitating the monitoring of these genetic statuses to guide drug selection. Additionally, some cancer cells harbor mutations in their signaling pathways (such as PI3K/AKT/mTOR) (208), indicating the potential need for combination therapies involving anti-angiogenic drugs and agents targeting these pathways. Lastly, the development of targeted therapies focuses on tumor-specific molecular features, such as particular gene mutations (209). These targeted agents can selectively affect tumor cells while minimizing impact on normal cells, exemplified by drugs like EGFR inhibitors and ALK inhibitors.

Initially, tumor genome sequencing (210) can be conducted. Through comprehensive genomic sequencing of patient tumor tissue, we can identify mutations, copy number variants, gene rearrangements, and other genomic alterations (211). These data are instrumental in defining the molecular characteristics of tumors, identifying driver mutations, and pinpointing potential drug targets (212, 213). By pairing a driver mutation with an appropriate drug, we can tailor treatments for molecularly complex and heterogeneous cancers using a combination of customized therapies (214). Song et al. (215) demonstrated for the first time that treatment plans for bispecific antibodies can be customized for advanced non-small cell lung cancer based on the genetic information of the stromal region, with the potential to predict treatment efficacy.

Additionally, we can perform a liquid biopsy, which provides non-invasive options for tumor detection and personalized therapy by detecting circulating tumor DNA (ctDNA) and other biomarkers in cells. Some studies have indicated that urine DNA methylation detection can facilitate early detection and recurrence monitoring of bladder cancer (216).

Moreover, we can develop individualized vaccines based on tumor-specific antigens to activate and enhance the patient’s immune response. The high tumor specificity and immunogenicity of these vaccines are considered the ultimate goal of tumor immunotherapy. New antigen-based dendritic cell (DC) vaccines represent a promising therapeutic modality. One investigator initiated a single-arm pilot study (ChiCTR-O NC-16009100, NCT02956551) using a personalized neoantigen peptide-pulsed autologous DC vaccine for lung cancer.

Furthermore, screening for biomarkers is crucial. Patients most likely to benefit from treatment can be selected based on their tumor biomarkers, such as PD-L1 expression, DNA repair defects (e.g., BRCA mutations), and fusion gene status. Lastly, a risk assessment can be performed by evaluating genetic susceptibility, family history, and other factors to customize surveillance and prevention strategies (217, 218).