{"title":"Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report.","authors":"Henghu Fang, Wei Yang, Qing Han, Rugang Zhao, Wei Zheng, Zejun Lu, Shanshan Wu, Qi Zhu, Jingjiao Li, Gaowa Guan, Juyi Wen","doi":"10.1097/CAD.0000000000001661","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001661","url":null,"abstract":"<p><p>Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed by China with independent intellectual property rights. Phase II clinical trials for advanced breast cancer are being approved by National Medical Products Administration for the treatment of advanced breast cancer. However, there is no report on the application in non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) mutation. This case is a patient with EGFR mutant stage IV NSCLC who has progressed after third-line targeted therapy. The fourth line was treated with utidelone combined with pabolizumab. The patient had progressed after targeted therapy with oxitinib, ametinib, and vometinib. Due to the patient's physical reasons, the traditional platinum drugs were not suitable, so the patient was treated with utidelone combined with pabolizumab. The curative effect was evaluated as SD after two cycles and progesterone receptor after four cycles. At present, it is still in the maintenance of reduction of utidelone combined with pabolizumab, and the tumor continues to shrink. Although peripheral neurotoxicity occurred during treatment, it improved after symptomatic treatment. The treatment of EGFR mutant stage IV NSCLC with utidelone combined with pabolizumab has good effect and mild adverse reactions.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-17DOI: 10.1097/CAD.0000000000001659
Chenliang Hou, Yanning Hu, Tao Zhang
{"title":"Research on curcumin mediating immunotherapy of colorectal cancer by regulating cancer associated fibroblasts.","authors":"Chenliang Hou, Yanning Hu, Tao Zhang","doi":"10.1097/CAD.0000000000001659","DOIUrl":"10.1097/CAD.0000000000001659","url":null,"abstract":"<p><p>The objective was to investigate curcumin's (Cur) function and associated molecular mechanisms in regulating tumor immunity in colon cancer. Primary cancer-associated fibroblasts (CAFs) from mouse CT26 colon cancer tumors were isolated. Validation of primary CAFs using immunofluorescence assay was done. Cell Counting Kit-8 experiments, real-time quantitative PCR (qPCR), and enzyme linked immunosorbent assay experiments were conducted to investigate how curcumin affected the growth and cytokine secretion functions of CAFs. The effect of curcumin on regulating PD-L1 expression on CT26 cells through CAFs in vitro was explored through coculture of CAFs and tumor cells, qPCR, and western blot experiments. A mouse colon cancer cell model was established in Balb/c nude mice to explore the effect of curcumin on colon tumor cells. Changes in the tumor microenvironment were detected by flow cytometry to explore the synergistic effect of curcumin combined with anti-PD-1 monoclonal antibody in the treatment of mouse colon cancer. In vitro, curcumin prevented the growth and TGF-β secretion of CT26 cells. At the same time, curcumin inhibited the secretion of TGF-β by CAFs, thereby downregulating the PD-L1 expression of CT26 cells. In vivo, curcumin combined with anti-PD-1 antibodies can further enhance the inhibitory effect of PD-1 antibodies on tumors and increase the number of tumor-suppressing immune cells in the tumor microenvironment, such as M1 macrophages and CD8 T cells, thus inhibiting tumors. Immune M2 macrophages, regulatory T cells, and other cells were reduced. In conclusion, curcumin reduces the expression of PD-L1 in colon cancer cells and improves the tumor immune microenvironment by inhibiting the proliferation of CAFs and the secretion of TGF-β. Curcumin and anti-PD-1 treatment have synergistic inhibitory effects on colon cancer.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-16DOI: 10.1097/CAD.0000000000001664
Qi Chen, Hong Zhang
{"title":"SMAC mimetic BV6 acts in synergy with mTOR inhibitor to increase cisplatin sensitivity in ovarian cancer.","authors":"Qi Chen, Hong Zhang","doi":"10.1097/CAD.0000000000001664","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001664","url":null,"abstract":"<p><p>The objective of this study is to observe the antitumor efficacy of the second mitochondria-derived activator of caspases (SMAC) mimetic bivalent smac mimetic (BV6) in combination with target of rapamycin (mTOR) inhibitor on DDP (cisplatin) sensitivity. Ovarian cancer cells were exposed to cisplatin, BV6, DDP + BV6, and DDP + BV6 + mTOR inhibitor Rapamycin. Using proteomics and bioinformatics, protein expression profiles in ovarian cancer were determined. Bagg Albino color nude mice were treated with DDP or BV6 alone or in combination, or BV6 + DDP + Rapamycin. The effects of different treatments on ovarian cancer cells and tumor growth were evaluated in vivo and in vitro. Proteomics and bioinformatics analysis revealed significant changes of protein kinase (AKT)/mTOR pathway. Consistently, western blot data indicated that AKT/mTOR axis was gradually activated in BV6-treated ovarian cancer cells and attenuated the cytotoxic effect of BV6. Functional assays showed that DDP or BV6 treatment alone significantly enhanced the sensitivity and inhibited the migration of ovarian cancer cells, but without any synergistic effects. In addition, combination with BV6 and mTOR inhibitor Rapamycin significantly decreased cell viability and inhibited migration of ovarian cancer cells exposed to DDP. Consistently, the xenograft model showed that co-treatment with Rapamycin with BV6 had significantly suppressed tumor growth and metastasis. Our study demonstrated that SMAC analogue BV6 exhibits a strong anticancer effect on ovarian cancer in vitro and in vivo. Combination with Rapamycin overcomes the activation of mTOR pathway by BV6 and increases the chemosensitivity to DDP. These data suggest a potential application of triple combination with DDP + BV6 + Rapamycin in clinical management of ovarian cancer.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-16DOI: 10.1097/CAD.0000000000001666
Mariam A Kidwani, Hasnaa Osama, Ahmed Hassan, Mohamed E A Abdelrahim
{"title":"Prophylactic role of pentoxifylline against paclitaxel-induced neuropathy among patients with breast cancer: a randomized-controlled trial.","authors":"Mariam A Kidwani, Hasnaa Osama, Ahmed Hassan, Mohamed E A Abdelrahim","doi":"10.1097/CAD.0000000000001666","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001666","url":null,"abstract":"<p><p>Paclitaxel-induced peripheral neuropathy (PN) is a significant clinical concern for which no approved treatment is currently available. The purpose of this trial was to investigate the neuro-prophylactic impact of pentoxifylline against paclitaxel-induced PN in patients diagnosed with breast cancer (BC). BC patients who were assigned to paclitaxel chemotherapy were randomly allocated to pentoxifylline or a control group for 12 weeks. The main outcomes included the assessment of PN incidence according to the defined Common Terminology Criteria for Adverse Events, quality of life (QoL) using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTx) scale, and neuropathic pain using the scale of self-reported Leeds Assessment for Neuropathic Symptoms and Signs (s-LANSS). The code of the clinical trial registration is NCT06562998. The current study included a total of 72 patients allocated into pentoxifylline arm (n = 35) and placebo arm (n = 37). By the 12th week, the prevalence of PN (grade 2 or 3) was significantly lower in the pentoxifylline arm 10/35 (28.6%) compared to 24/37 (64.9%) of the controls (P value = 0.016). The total FACT/GOG-NTx score indicated a considerably worse QoL in the control group [98.18 (10.2) vs. 81.43 (14.8) for pentoxifylline and the control group, respectively, P < 0.001] with a mean difference of -16.75 [95% confidence interval (CI): -23.97 to -9.53]. S-LANSS scale showed significantly higher scores after 6 weeks [13.72 (5.86) vs. 17.52 (3.16), P = 0.002] and 12 weeks [17.84 (4.25) vs. 23.80 (1.00), P < 0.001] for pentoxifylline and control group, respectively. In conclusion, the use of pentoxifylline showed a significant reduction in paclitaxel-induced PN, which improved their QoL.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-01Epub Date: 2024-06-28DOI: 10.1097/CAD.0000000000001635
Santiago Cabezas-Camarero, María Nieves Cabrera-Martín, María Cruz Iglesias-Moreno, Pedro Pérez-Segura
{"title":"Hyper-late major response after 5 years of nivolumab: role of treatment beyond progression in head and neck cancer.","authors":"Santiago Cabezas-Camarero, María Nieves Cabrera-Martín, María Cruz Iglesias-Moreno, Pedro Pérez-Segura","doi":"10.1097/CAD.0000000000001635","DOIUrl":"10.1097/CAD.0000000000001635","url":null,"abstract":"<p><p>Patients with recurrent/metastatic (R/M) platinum-refractory squamous cell carcinoma of the head and neck (SCCHN) have fewer treatment options and harbor an especially poor prognosis. Maintaining treatment with anti-PD1 agents beyond response evaluation criteria in solid tumors-defined disease progression (TBP) has been shown to be efficacious in several solid tumors, including head and neck cancer. We present the case of a platinum-refractory locally recurrent, PD-L1-negative hypopharyngeal carcinoma, that received second-line nivolumab which was then maintained beyond progression under the following criteria: no Eastern Cooperative Oncology Group performance status deterioration, no rapidly progressive disease, no severe toxicity, and evidence of overall treatment benefit. The patient achieved a partial response 8 months after starting second-line nivolumab, with progressive disease at 26 months, then followed by the first TBP with nivolumab lasting for 15 months due to a new tumor progression. A second TBP with nivolumab lasting for 7 months, was followed by a third TBP with nivolumab for 12 months and achieving a major tumor response. Treatment is still ongoing 60 months after starting nivolumab, with excellent tolerance to therapy. Maintaining anti-PD1 agents beyond progression is an efficacious treatment option for patients with R/M SCCHN, that may achieve very durable disease control and even late major responses.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"875-877"},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-01Epub Date: 2024-08-07DOI: 10.1097/CAD.0000000000001636
Francesco Vitali, Susanne Merkel, Christoph Schubart, Axel Schmid, Markus Eckstein, Robert Stöhr, Stephan Kersting, Arndt Hartmann, Robert Grützmann, Axel Wein
{"title":"Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.","authors":"Francesco Vitali, Susanne Merkel, Christoph Schubart, Axel Schmid, Markus Eckstein, Robert Stöhr, Stephan Kersting, Arndt Hartmann, Robert Grützmann, Axel Wein","doi":"10.1097/CAD.0000000000001636","DOIUrl":"10.1097/CAD.0000000000001636","url":null,"abstract":"<p><p>Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n = 25. RAS mutation: n = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n = 25. Complete response: n = 0, partial response: n = 14 (56%), stable disease: n = 8 (32%), progressive disease: n = 3 (12%), early tumor shrinkage: n = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"844-851"},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-01Epub Date: 2024-07-15DOI: 10.1097/CAD.0000000000001639
Sare Hosseini, Sara Rahsepar, Sara Naghipour, Sepideh Elyasi
{"title":"Is oral nano-curcumin formulation a safe and effective measure for preventing cisplatin-induced nephrotoxicity in cancer patients?","authors":"Sare Hosseini, Sara Rahsepar, Sara Naghipour, Sepideh Elyasi","doi":"10.1097/CAD.0000000000001639","DOIUrl":"10.1097/CAD.0000000000001639","url":null,"abstract":"<p><p>Nephrotoxicity is one of the most important complications in cancer patients under treatment with cisplatin-containing regimens. Curcumin, as the most important active component of Curcuma longa, is an antioxidant and anti-inflammatory compound. In this clinical trial, we assessed the preventive effect of nano-curcumin oral formulation against cisplatin-induced nephrotoxicity in cancer patients. In this triple-blind clinical trial 30 cancer patients on cisplatin were randomly included in the treatment group, receiving nano-curcumin 40 mg capsules ( n = 15) or the placebo group ( n = 15) twice a day during four chemotherapy courses. Kidney function was measured at the beginning of the study and then at the end of each course of chemotherapy. There was no significant difference in acute kidney injury occurrence rate and creatinine and blood urine nitrogen serum levels between the treatment and placebo groups at the end of each chemotherapy course ( P value >0.05). Just at the end of the first course, the difference was close to significant ( P = 0.055). We also found no difference in mortality and recurrence rate in an average 30-month follow-up. Nano-curcumin in the prescribed dose and duration was not effective in preventing cisplatin-induced nephrotoxicity in cancer patients in comparison with the placebo. Further studies with larger sample size using different doses and duration of nano-curcumin are recommended.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"859-866"},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-01Epub Date: 2024-07-08DOI: 10.1097/CAD.0000000000001634
Alicia Martín Roldán, Carolina Alarcón-Payer, María Del Mar Sánchez Suárez, Alberto Jiménez Morales
{"title":"Dermatological toxicity associated with the use of gilteritinib in relapsed acute myeloid leukemia with FLT3 mutation: a case report.","authors":"Alicia Martín Roldán, Carolina Alarcón-Payer, María Del Mar Sánchez Suárez, Alberto Jiménez Morales","doi":"10.1097/CAD.0000000000001634","DOIUrl":"10.1097/CAD.0000000000001634","url":null,"abstract":"<p><p>We present a case of a patient diagnosed with FLT3 mut+ acute myeloid leukemia with FLT3 and NMP1 mutations who did not respond to standard induction and consolidation treatment with chemotherapy. Due to the FLT3mut+ gene mutation and intermediate cytogenetic risk, treatment with gilteritinib is requested. After treatment she experienced a neutrophilic dermatosis and granuloma annulare that was resolved with gilteritinib dose reduction and specific treatment in coordination with the dermatology department.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"872-874"},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-01Epub Date: 2024-07-23DOI: 10.1097/CAD.0000000000001638
Nesime İnci Güner, Ömer Dizdar, Alev Türker, Aygin Bayraktar-Ekincioglu
{"title":"Rituximab-induced leukocytoclastic vasculitis in a patient with low-grade orbital B-cell lymphoma: a case report.","authors":"Nesime İnci Güner, Ömer Dizdar, Alev Türker, Aygin Bayraktar-Ekincioglu","doi":"10.1097/CAD.0000000000001638","DOIUrl":"10.1097/CAD.0000000000001638","url":null,"abstract":"<p><p>Rituximab is an anti-CD20 chimeric murine/human mAb mainly used to treat certain types of lymphoproliferative malignancies and autoimmune diseases. Although it has been used in the treatment of vasculitis in recent years, it rarely triggers severe vascular skin reactions such as leukocytoclastic vasculitis (LCV). Physicians should be aware of this rare adverse event that requires discontinuation of rituximab, which can occur days or even weeks after rituximab treatment. Here, we report a case of LCV observed in a patient with low-grade orbital B-cell lymphoma treated with weekly rituximab and local radiotherapy. In our case, discontinuation of rituximab and initiation of oral methylprednisolone therapy were sufficient to achieve complete resolution of the LCV.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"878-881"},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-Cancer DrugsPub Date : 2024-10-01Epub Date: 2024-07-01DOI: 10.1097/CAD.0000000000001630
Yaping Long, Zizheng Xu, Jing Yu, Xiao Hu, Yu Xie, Xianxian Duan, Ning Li, Yan Yan, Yue Wang, Junfang Qin
{"title":"Targeting xCT with sulfasalazine suppresses triple-negative breast cancer growth via inducing autophagy and coordinating cell cycle and proliferation.","authors":"Yaping Long, Zizheng Xu, Jing Yu, Xiao Hu, Yu Xie, Xianxian Duan, Ning Li, Yan Yan, Yue Wang, Junfang Qin","doi":"10.1097/CAD.0000000000001630","DOIUrl":"10.1097/CAD.0000000000001630","url":null,"abstract":"<p><p>There is a substantial unmet need for effective treatment strategies in triple-negative breast cancer (TNBC). Recently, renewed attention has been directed towards targeting glutamine (Gln) metabolism to enhance the efficacy of cancer treatment. Nonetheless, a comprehensive exploration into the mechanistic implications of targeting Gln metabolism in TNBC is lacking. In this study, our objective was to probe the sensitivity of TNBC to alterations in Gln metabolism, using representative TNBC cell lines: MDA-MB-231, MDA-MB-468, and 4T1. Through an integration of bioinformatics, in-vitro, and in-vivo investigations, we demonstrated that sulfasalazine (SAS), like erastin (a known xCT inhibitor), effectively suppressed the expression and transport function of xCT, resulting in a depletion of glutathione levels in MDA-MB-231 and MDA-MB-468 cells. Furthermore, both xCT knockdown and SAS treatment demonstrated the promotion of cellular autophagy. We unveiled a positive correlation between xCT and the autophagy-related molecule p62, their co-expression indicating poor survival outcomes in breast cancer patients. In addition, our research revealed the influence of SAS and xCT on the expression of proteins regulating cell cycle and proliferation. Treatment with SAS or xCT knockdown led to the inhibition of MYC, CDK1, and CD44 expression. Significantly, the combined administration of SAS and rapamycin exhibited a synergistic inhibitory effect on the growth of transplanted breast tumor in mouse models constructed from murine-derived 4T1 cells. Taken together, our findings suggested the potential and clinical relevance of the SAS and rapamycin combination in the treatment of TNBC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"830-843"},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}