Oral Cancer Therapy Research Articles

Hybrid CAR γδ T Cells for Oral Cancer Therapy: Enhanced Safety and Targeted Efficacy

Hybrid CAR γδ T Cells for Oral Cancer Therapy: Enhanced Safety and Targeted Efficacy

Impact of Patient Personality on Adherence to Oral Anticancer Medications: An Opportunity?

Adherence to prescribed oral anticancer therapy is an important determinant of patient outcomes, including progression-free and overall survival. While many factors (eg, medication side effects and out-of-pocket costs, problems with insurance authorization, and timely medication refills) can affect adherence, one that is relatively unexplored is the impact of a patient's attitude and personality. Patient personality influences medication adherence and persistence in nonmalignant chronic conditions such as cardiovascular disease and diabetes. In breast cancer and chronic myeloid leukemia, studies suggest that personality also affects adherence to oral chemotherapy which can be targeted to improve adherence. In this viewpoint, we highlight the opportunity of incorporating patient personality as interventions to oral cancer therapy adherence and discuss current barriers to implementation.

Natural compounds targeting miRNAs: a novel approach in oral cancer therapy.

Oral cancer (OC) is a significant global health issue, with high rates of both mortality and morbidity. Conventional treatments, including surgery, radiation, and chemotherapy, are commonly used, but they often come with serious side effects and may not fully eliminate cancer cells, resulting in recurrence and resistance to treatment. In recent years, natural products derived from plants and other biological sources have gained attention for their potential anticancer properties. These compounds offer advantages such as lower toxicity compared to traditional chemotherapy. Notable natural compounds like quercetin, berberine, curcumin, andrographolide, nimbolide, ovatodiolide, and cucurbitacin B have demonstrated effectiveness in inhibiting OC cell growth by targeting various signaling pathways involved in cancer progression. Recent breakthroughs in molecular biology have highlighted the crucial role of microRNAs (miRNAs) in the development of OC. Targeting dysregulated miRNAs with natural products offers a promising strategy for treating the disease. Natural compounds exert anticancer effects by influencing both altered cellular signaling pathways and miRNA expression profiles. This study aims to explore the role of miRNAs as potential molecular targets in OC and to investigate how natural products may regulate these miRNAs. Additionally, this review will shed light on the therapeutic potential of phytochemicals in modulating miRNA expression and their significance in OC treatment.

Non-receipt of targeted and immunotherapies in diverse patients with metastatic cancers.

93 Background: The rapid evolution of molecularly targeted kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of metastatic cancer, coupled with high drug costs, raises potential for unwarranted variation in patient management. We evaluated correlates of non-receipt of TKIs and ICIs in a diverse, population-based sample of patients with metastatic non-small cell lung cancer (NSCLC), kidney and bladder (GU) cancer, and melanoma. Methods: We identified 2240 patients diagnosed in 2019 with metastatic NSCLC, GU cancer, or melanoma and reported to the Georgia or Los Angeles SEER registries. Using SEER registry data, we linked all patients to a managing oncology physician. We collected data from the managing physician regarding receipt of TKIs and ICIs. We used bivariate analyses and multivariable logistic regression models to assess associations between non-receipt of TKIs and ICIs and patient-level factors. Results: We present results for a preliminary sample (N=894). About half (55%) of the patients had NSCLC, 31% had GU cancer, and 14% had melanoma. The mean age was 62 (SD 12); 59% were male; 65% were White, 16% were Black, 11% were Hispanic, and 7% were Asian; 52% had Medicare, 29% had private insurance, 9% had Medicaid, and 4% had no insurance; 89% resided in urban areas, 11% resided in rural areas. 22% lived in a census tract area with >20% of the population living below the poverty level. The Table shows that in bivariate analyses, non-receipt of TKIs was associated with NSCLC, older age, male sex, non-white race, and non-private or no insurance (all p<0.05). After adjustment, non-receipt of TKIs was associated with NSCLC, older age, male sex, and race. Asian and Hispanic patients had lower rates of non-receipt, and Black patients had higher rates. In bivariate analyses, non-receipt of ICIs was associated with NSCLC and GU cancer (p=0.004); this association remained significant after adjustment. Conclusions: Non-receipt of TKIs was associated with important non-clinical factors including race and sex. Non-receipt of ICIs was associated only with cancer type. These findings suggest that policy-relevant factors such as out-of-pocket costs for oral cancer therapies and differential access to molecular sequencing may contribute to unwarranted variation in receipt of TKIs. Bivariate analyses of non-receipt. Did not Receive TKI Did not Receive ICI % P % P Cancer type NSCLC GU Melanoma 786572 0.002 313015 0.004 Age <50 50-64 65-74 75-84 85+ 5471757986 <0.001 2625302940 0.385 Sex Male Female 7670 0.048 2631 0.085 Race & Ethnicity White Black Hispanic Asian Other 7579655860 0.002 2329312927 0.981 Marital Status Married Unmarried 7373 0.645 2630 0.158 Insurance Medicare Medicaid Private Other government None 7075637080 <0.001 3130215031 0.101 Geography Urban Rural 7375 0.784 2826 0.567 % population below poverty level 0-5% 5-<10% 10-<20% 20-100% 69717774 0.314 29273222 0.138

Enhanced Therapeutic Efficacy of Gold Nanoparticle-Enhanced Laser Therapy for Oral Cancer: A Promising Photothermal Approach.

Introduction: Laser therapy employs a concentrated and slender light beam to eliminate or eradicate cancerous cells and pre-cancerous abnormalities. The specific wavelength of 808 nm light is preferentially absorbed by tumor cells compared to healthy cells. This study aimed to assess the combined therapeutic impact of laser and gold, given that gold exhibits photothermal properties when exposed to laser radiation. Methods: In this in vitro study, two cell lines, namely healthy HuGu cells (human gingival fibroblast cells) and head and neck cancer cells (HN-5), were obtained from the Pasteur Institute. The effect of the laser diode with a density of 3 J/cm2 and wavelength of 808 nm on the proliferation and the survival rate of oral squamous cell carcinoma (HN-5) and human gingival fibroblast (HUGU) was assessed in 60seconds. MTT assay, DAPI test, and trypan blue staining were used to determine the growth and proliferation of HN-5 and HUGU cell lines. Results: Findings showed that the laser diode along with gold decreased the rate of proliferation and survival cells in HN-5 compared to healthy cells. The changes in the cell population treated with gold and laser diode 808 were insignificant. Conclusion: Findings reveal that using a low-power laser can effectively inhibit the growth of oral cancer cells. It seems that photothermal therapy is a novel approach to oral cancer therapy.

The role of emodin in oral cancer therapy: from traditional medicine to modern nanotechnology

The role of emodin in oral cancer therapy: from traditional medicine to modern nanotechnology

AT11-guided liposomes for oral cancer cells: From characterization towards in vitro evaluation

The increasing prevalence of oral cancers, particularly those attributed to human papillomavirus infection, along with the associated drawbacks of conventional therapies, has spurred research into more effective treatment modalities. Liposomes have emerged as a potential strategy to improve the delivery of anticancer molecules to the cells of interest. However, functionalizing these nanoparticles with targeting agents could significantly enhance their selectivity. A prospective approach involves the incorporation of aptamers, which facilitate drug accumulation within cancer cells. Among these, the AT11 aptamer has garnered attention due to its improved toxicity and high affinity to nucleolin, making it a promising targeting moiety. Therefore, we propose to use AT11 for liposomes’ functionalization, to enhance the selectivity of C8, a potential anticancer compound, specifically targeting oral cancer cells. Thus, we produced liposomes (empty or C8-associated) by ethanol injection method and, then, proceeded with their functionalization with AT11-TEG-Cholesteryl. The resulting liposomes were characterized by dynamic light scattering and hydrodynamic diameters of 130–136 nm were obtained. Additionally, the effect of the produced liposomes on the viability of squamous cell carcinoma of the tongue (UPCI-SCC-154) and nonmalignant (Het1A) cells was determined, by MTT assay. It was demonstrated that the viability of cells treated with empty liposomes was almost unaffected until the 53.6 μg/mL concentration. After treating the cells with C8-associated liposomes, both cell lines showed a dose-response effect. Moreover, the AT11-functionalization of the obtained C8-associated liposomes enhanced the selectivity of the liposomes towards oral cancer cell line, as observed by the MTT assay (43.2 % in UPCI-SCC-154 versus 79.4 % in Het1A) and confocal microscopy. Furthermore, the anticancer potential of AT11 C8-associated liposomes was evaluated in terms of proliferation (ki67 positive cells), cell death (propidium iodide internalization in non-permeabilized cells and caspase-3 activity), migration (cell scratch assay) and invasion. Overall, the produced liposomes decreased tongue cancer cell proliferation (53.6 % versus 99.4 %), migration (from 24.6 % to −3.8 %) and invasion (to 19 %) and induced cell death (11.6-fold increase in propidium iodide positive cells, and a 140 % of caspase-3 activity). These findings suggest that the AT11 C8-associated liposomes are promising drug carriers for oral cancer therapy.

Unraveling the key role of chromatin structure in cancer development through epigenetic landscape characterization of oral cancer

Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.

Innovative Progress: Artificial Intelligence in the Realm of Oral Cancer

In recent years, there has been a notable increase in the global incidence of oral cancer, leading to significant morbidity and mortality, especially when diagnosed at advanced stages. The integration: In recent years, there has been a notable increase in the global incidence of oral cancer, leading to significant morbidity and mortality, especially when diagnosed at advanced stages. The integration of technology holds great promise for early detection and diagnosis, facilitating improved patient management for clinicians. The emergence of artificial intelligence (AI) presents a potential breakthrough in oral cancer screening, as it can meticulously analyze vast datasets from various imaging modalities, offering valuable support in the field of oncology. This review focuses on a spectrum of AI techniques utilized for early detection and diagnosis of oral cancer. Additionally, AI techniques may be employed for the effective treatment of oral cancer. Using the abundance of information acquired, this article provides an in-depth overview and discussion of AI's value and benefits in oral cancer screening, early detection, disease prediction, and therapy, among other areas. Furthermore, it identifies present limits and forecasts the hopeful future of AI in oral cancer research.

Induction of Endoplasmic Reticulum Stress and Aryl Hydrocarbon Receptor Pathway Expression by Blue LED Irradiation in Oral Squamous Cell Carcinoma.

Photobiomodulation therapy, as an emerging treatment modality, has been widely used in dentistry. However, reports on blue light therapy for oral cancer are scarce. This study investigated the effects of 457 and 475 nm LED irradiation on SCC-25 cells and explored the potential mechanisms underlying the impact of blue light. Both wavelengths were found to inhibit cell viability, induce oxidative stress, and cause cell cycle arrest without leading to cell death. Notably, the inhibitory effect of 457 nm blue light on cell proliferation was more sustained. Transcriptome sequencing was performed to explore the underlying mechanisms, revealing that blue light induced endoplasmic reticulum stress in SCC-25 cells, with 457 nm light showing a more pronounced effect. Moreover, 457 nm blue light upregulated the expression of the aryl hydrocarbon receptor pathway, indicating potential therapeutic prospects for the combined use of blue light and pharmacological agents.

Dietary plants for oral cancer prevention and therapy: A review of preclinical and clinical studies.

Oral cancer is a disease with high mortality and rising incidence worldwide. Although fragmentary literature on the anti-oral cancer effects of plant products has been published, a comprehensive analysis is lacking. In this work, a critical and comprehensive evaluation of oral cancer preventative or therapeutic effects of dietary plants was conducted. An exhaustive analysis of available data supports that numerous dietary plants exert anticancer effects, including suppression of cell proliferation, viability, autophagy, angiogenesis, invasion, and metastasis while promoting cell cycle arrest and apoptosis. Plant extracts and products target several cellular mechanisms, such as the reversal of epithelial-to-mesenchymal transition and the promotion of oxidative stress and mitochondrial membrane dysfunction by modulation of various signaling pathways. These agents were also found to regulate cellular growth signaling pathways by action on extracellular signal-regulated kinase and mitogen-activated protein kinase, inflammation via modulation of cyclooxygenase (COX)-1, COX-2, and nuclear factor-κB p65, and metastasis through influence of cadherins and matrix metalloproteinases. In vivo studies support these findings and demonstrate a decrease in tumor burden, incidence, and hyperplastic and dysplastic changes. Clinical studies also showed decreased oral cancer risk. However, high-quality studies should be conducted to establish the clinical efficacy of these plants. Overall, our study supports the use of dietary plants, especially garlic, green tea, longan, peppermint, purple carrot, saffron, tomato, and turmeric, for oral cancer prevention and intervention. However, further research is required before clinical application of this strategy.

Cascade Hydroxyl Radical-Generating and Ferroptosis-Inducing Nanofiber System for the Therapy of Oral Squamous Cell Carcinoma.

Nanofiber (NF) membrane systems that can provide cascade catalytic reaction and ferroptosis induction were developed for oral cancer therapy. Glucose oxidase (GOx) and aminoferrocene (AF) were introduced into the NF system for glucose deprivation/H2O2 generation and OH radical generation, respectively. GOx offers starvation therapy and AF (including iron) provides chemodynamic therapy/ferroptosis for combating oral cancer. GOx (water-soluble) and AF (poorly water-soluble) molecules were successfully entrapped in the NF membrane via an electrospinning process. GOx and AF were incorporated into the polyvinyl alcohol (PVA)-based NF, resulting in PVA/GOx/AF NF with fast disintegration and immediate drug-release properties. In oral squamous cell carcinoma (YD-9 cells), the PVA/GOx/AF NF group exhibited higher cytotoxicity, antiproliferation potential, cellular ROS level, apoptosis induction, lipid ROS level, and malondialdehyde level compared to the other NF groups. The electrospun PVA/GOx/AF NF can be directly applied to oral cancer without causing pain, offering starvation/chemodynamic therapy and ferroptosis induction.

MRI tumour volumetry as a new staging tool in diagnosis and therapy of oral cancer

MRI tumour volumetry as a new staging tool in diagnosis and therapy of oral cancer

Unlocking the Therapeutic Potential of Oral Cancer Stem Cell-Derived Exosomes.

Oral cancer (OC) presents a significant global health burden with rising incidence rates. Despite advancements in diagnosis and treatments, the survival rate for OC patients, particularly those with advanced or recurrent disease, remains low at approximately 20%. This poor prognosis is often due to a small population of cancer stem cells (CSCs) that are capable of self-renewal and immune evasion, playing pivotal roles in proliferation, tumor initiation, progression, metastasis, and therapy resistance. Exosomes, which are nano-sized extracellular vesicles (EVs), have emerged as crucial mediators of cell-to-cell communication within the tumor microenvironment (TME). These vesicles carry diverse molecules such as DNA, RNA, proteins, lipids, and metabolites, influencing various cellular processes. Emerging evidence suggests that CSC-derived EVs significantly promote tumor progression and metastasis and maintain the balance between CSCs and non-CSCs, which is vital for intracellular communication within the TME of oral cancer. Recent reports indicate that oral cancer stem cell-derived EVs (OCSC-EVs) influence stemness, immune evasion, metastasis, angiogenesis, tumor reoccurrence, and drug resistance. Understanding OCSC-EVs could significantly improve oral cancer diagnosis, prognosis, and therapy. In this mini-review, we explore OCSC-derived exosomes in oral cancer, examining their potential as diagnostic and prognostic biomarkers that reflect CSC characteristics, and delve into their therapeutic implications, emphasizing their roles in tumor progression and therapy resistance. However, despite their promising potential, several challenges remain, including the need to standardize isolation and characterization methods and to elucidate exosome-mediated mechanisms. Thus, a comprehensive understanding of OCSC-EVs could pave the way for innovative therapeutic strategies that have the potential to improve clinical outcomes for OC patients.

Lactiplantibacillus plantarum exerts anticancer effects and increase the chemosensitivity of 5-fluorouracil against oral cancer cells in vitro

Introduction: Probiotics are used to provide health benefits and can improve the immune response. They can also target cancer cells directly with anticancer effects through various mechanisms. In this study, Lactiplantibacillus plantarum (basonym: Lactobacillus plantarum) strain MCC 3016 and its postbiotic metabolites/cell free supernatant (CFS) were used against Cal27 oral cancer cells in vitro. Methods: Standard assays were employed to investigate the effect of Lpb. plantarum on cell viability, proliferation, migration, and clonogenicity of Cal27 cells. The mechanism of action was assessed by measuring the levels of reactive oxygen species (ROS), interleukins (IL)-6 and IL-8, tumor necrosis factor-α (TNF-α), as well as the expression of Ki67, vascular endothelial growth factor (VEGF), p53 and caspase-3. Further, the effect of Lpb. plantarum and its CFS on the cytotoxicity of chemotherapy drug 5-fluorouracil (5-FU) was evaluated using cell viability assays. Results: Cal27 cells treated with Lpb. plantarum and its CFS showed a significant decrease (P < 0.01) in cell viability, proliferation, migration, and clonogenicity, along with increased levels of ROS and induced apoptosis. It significantly reduced IL-6, IL-8, TNF-α, and VEGF levels and upregulated p53 and caspase-3 expression. The postbiotic metabolites also showed similar effects on Cal27 cells. Furthermore, the cytotoxic effect of 5-FU on Cal27 cells was enhanced by Lpb. plantarum and its CFS treatment. Conclusion: Lpb. plantarum MCC 3016 and its postbiotic metabolites exhibited promising anticancer effects on oral cancer cells and improved drug efficacy, demonstrating their potential therapeutic value in oral cancer therapy.

Innovative polysaccharide-based hydrogels: a promising vehicle for bioactive compounds in oral cancer therapy

Innovative polysaccharide-based hydrogels: a promising vehicle for bioactive compounds in oral cancer therapy

Jasminum grandiflorum oral gel as an add-on to standard of care in radiation induced grade 2 oral mucositis - an open label pilot clinical trial

BackgroundRadiation-induced oral mucositis is one of the most critical dose-limiting toxicities associated with radiation therapy for oral cancer which can result in treatment interruption and compromise the quality of the life of cancer patients. Jati (Jasminum grandiflorum) is used in Ayurveda to treat oral conditions like stomatitis and mouth ulcers. ObjectiveTo test the feasibility of Jati oral gel as an add on therapy in grade 2 radiation-induced oral mucositis. Materials and methodsA prospective, open-label, non-randomised pilot trial was conducted on 20 patients with grade 2 radiation-induced oral mucositis at a tertiary cancer hospital. The control group received sodium bicarbonate mouthwash 4–5 times daily as the standard of care, while the intervention arm also received Jati oral gel twice daily. We used the ImageJ software for objective assessment and the Visual Analogue Scale for subjective pain assessment. The study was continued for 15 days or until the mucositis progressed to grade 3 or resolved to grade 1. ResultThere was a significant reduction in the mean pain score and mean area of mucositis in the intervention group compared to the control group. ConclusionJati oral gel is a suitable medicament as an add-on therapy in managing grade 2 radiation-induced oral mucositis.

In silico Screening and in vitro Cytotoxicity Study of Achyranthes aspera Phytochemicals Against Oral Cancer: A Possible Step towards the Development of Anti-cancer Agents.

Oral cancer poses a significant threat to public health worldwide. In addition, because many chemotherapy treatments have negative side effects, natural herbs may be beneficial for oral cancer therapy. Achyranthes aspera (AA), a potential medicinal herb, exerts various pharmacological and biochemical activities. The present study aimed to predict the anti-oral cancer potential of AA using in silico tools and cell death by in vitro testing. A total of fourteen bioactive constituents from AA herb were selected using phytochemical databases. The toxicity of AA herb extract was analysed through MTT assay against oral carcinoma A253 cell line. The binding activities of the phytocomponents against serine/ threonine-specific protein kinases isoforms, namely Akt1 (PDB ID: 3qkk) and Akt2 (PDB ID: 2jdo) proteins, were analysed using Discovery Studio 2021 and PyRx docking software. Cell viability data revealed that AA extract decreased the viability and reduced the number of live cells of the oral carcinoma A253 cell line in a dose-dependent manner. The halfmaximal concentration (IC50) value of AA was assessed as 204.74 μg/ml. Based on binding affinity, saponin C (-CDOCKER energy = -77.9862), oleanolic acid (-CDOCKER energy = - 49.4349), spinasterol (-CDOCKER energy = -38.1246), 36,47-dihydroxyhenpentacontan-4-one (-CDOCKER energy = -32.4386), and 20-hydroxyecdysone (-CDOCKER energy = -31.9138) were identified as the best compounds against Akt1, while, compounds saponin C (-CDOCKER energy = -134.412), oleanolic acid (-CDOCKER energy = -90.0846), spinasterol (-CDOCKER energy = -78.3213), 20-hydroxyecdysone (-CDOCKER energy = -80.1049), and ecdysone (- CDOCKER energy = -73.3885) were identified as Akt2 inhibitors. These top compounds fulfilled drug score values, pharmacokinetic and physicochemical characteristics, and druglikeness parameters. The present findings reveal that the lead phytomolecules of AA could be effective and developed as a prospective drug against oral cancer.

"Abraxane-Like" Radiosensitizer for In Situ Oral Cancer Therapy.

Radiotherapy plays a vital role in cancer therapy. However, the hypoxic microenvironment of tumors greatly limits the effectiveness, thus it is crucial to develop a simple, efficient, and safe radiosensitizer to reverse hypoxia and ameliorate the efficacy of radiotherapy. Inspired by the structure of canonical nanodrug Abraxane, herein, a native HSA-modified CaO2 nanoparticle system (CaO2-HSA) prepared by biomineralization-induced self-assembly is developed. CaO2-HSA will accumulate in tumor tissue and decompose to produce oxygen, altering the hypoxic condition inside the tumor. Simultaneously, ROS and calcium ions will lead to calcium overload and further trigger immunogenic cell death. Notably, its sensitizing enhancement ratio (SER = 3.47) is much higher than that of sodium glycididazole used in the clinic. Furthermore, in animal models of in situ oral cancer, CaO2-HSA can effectively inhibit tumor growth. With its high efficacy, facile preparation, and heavy-metal free biosafety, the CaO2-HSA-based radiosensitizer holds enormous potential for oral cancer therapy.

Efficacy of Cisplatin-CXCR4 Antagonist Combination Therapy in Oral Cancer.

Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin-AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC.