Ning Li, Lu Yang, Zixuan Zhao, Tian Du, Gehao Liang, Na Li, Jun Tang
{"title":"Antibody-drug conjugates in breast cancer: current evidence and future directions.","authors":"Ning Li, Lu Yang, Zixuan Zhao, Tian Du, Gehao Liang, Na Li, Jun Tang","doi":"10.1186/s40164-025-00632-9","DOIUrl":"10.1186/s40164-025-00632-9","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are a rapidly evolving class of antitumor drugs and have already revolutionized the treatment strategy of many hematologic and solid cancers. So far, trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) are the four ADCs that have been approved by US food and drug administration (FDA) in treatment of breast cancer, and SKB264 has been approved by Chinese national medical products administration (NMPA). Many ADCs for treatment of breast cancer are currently being tested in late-phase clinical trials, with several encouraging results achieved recently. However, major issues arise during the use of ADCs, including emergence of acquired resistance, occurrence of treated-related toxicities, and identification of biomarkers of response and resistance. ADCs are being increasingly tested in combination with other agents, and novel next-generation ADC development is progressing rapidly. A better understanding of the design and development of ADCs will promote ADC development for cancer treatment. In this review, we aim to provide a broad overview of the design and the recent advances of ADCs in breast cancer. We also propose several notable future directions of ADCs in treatment of breast cancer.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"41"},"PeriodicalIF":9.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Theresa Kaeuferle, Maximilian Zwermann, Nadine Stoll, Paulina Ferrada-Ernst, Lena Jablonowski, Reinhard Zeidler, Semjon Willier, Dana Stenger, Abdallah Yassin, Renata Stripecke, Tobias Feuchtinger
{"title":"All-in-one CRISPR/Cas-engineered glucocorticoid-receptor knock-out EBV-gp350-CAR knock-in T cells are potent and resistant to dexamethasone.","authors":"Theresa Kaeuferle, Maximilian Zwermann, Nadine Stoll, Paulina Ferrada-Ernst, Lena Jablonowski, Reinhard Zeidler, Semjon Willier, Dana Stenger, Abdallah Yassin, Renata Stripecke, Tobias Feuchtinger","doi":"10.1186/s40164-025-00631-w","DOIUrl":"10.1186/s40164-025-00631-w","url":null,"abstract":"<p><strong>Background: </strong>Epstein-Barr virus (EBV) reactivation in immunocompromised patients and post-transplantation is associated with morbidity, mortality and with the onset of a variety of malignant diseases. Adoptive T-cell therapies have emerged as promising therapeutic options, but post-transplant immunosuppression jeopardizes the protective anti-EBV immune surveillance by adoptively transferred T cells.</p><p><strong>Methods: </strong>Using an all-in-one CRISPR/Cas-mediated approach, we inserted an anti-EBV (gp350) CAR into the T-cell receptor (TRAC) locus and simultaneously knocked-out the glucocorticoid receptor (GR) on a good manufacturing practice (GMP)-compatible platform.</p><p><strong>Results: </strong>CAR knock-in (CAR<sup>KI</sup>) was confirmed in primary human T cells on genetic and on protein level with a mean efficiency of 41%. With 83%, additional GR knock-out was highly efficient in CAR<sup>KI</sup> cells. On a functional level CAR<sup>KI</sup>GR<sup>KO</sup> T cells showed target-specific potency in terms of cytokine secretion patterns, proliferative capacity and cytotoxic activity against gp350-expressing target cells. Further, CAR<sup>KI</sup>GR<sup>KO</sup> T cells were insensitive to dexamethasone treatment and maintained T-cell functionality. In contrast, CAR<sup>KI</sup>GR<sup>KO</sup> T cells were sensitive to the GR-independent immunosuppressant cyclosporine A (CsA), thereby providing a rescue treatment for patients in case of safety issues.</p><p><strong>Conclusions: </strong>The study lays the proof-of-concept for virus-free all-in-one GMP-manufacturing of glucocorticoid-resistant CAR T-cell products. Further, the glucocorticoid-resistant gp350-CAR T cells can provide a future therapeutic option for high-risk post-transplant patients with EBV-reactivations or patients with EBV-associated pathologies requiring steroid treatment.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"40"},"PeriodicalIF":9.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disparities in the incidence, mortality and disability-adjusted life years of 33 early-onset cancer groups globally, 2012-2021: a systematic analysis.","authors":"Wenxin Yan, Min Liu, Wenzhan Jing, Liangyu Kang, Ning Zhang, Haoran Sun, Jinyu He, Zhongdan Chen, Jue Liu, Wannian Liang, Jiahong Dong","doi":"10.1186/s40164-025-00634-7","DOIUrl":"10.1186/s40164-025-00634-7","url":null,"abstract":"<p><strong>Background: </strong>The global cancer burden is rising, with early-onset cancers becoming more prevalent. We aimed to investigate the burden, trend and population disparity in 33 early-onset cancers from 2012 to 2021.</p><p><strong>Methods: </strong>Annual incidence, death, and disability-adjusted life years (DALY) numbers and rates for early-onset (15-49 years) cancer groups were calculated from Global Burden of Diseases (GBD) 2021 dataset, covering 2012-2021 across global, five SDI groupings, and 204 countries and territories. Estimated annual percentage change (EAPC) in the incidence, mortality and DALY rates was calculated to quantify temporal trends, while spearman correlation analysis was used to examine the correlation between rates, EAPC and SDI.</p><p><strong>Results: </strong>In 2021, there were 2.65 million new early-onset cancer cases excluding non-melanoma skin cancer (NMSC), resulting in 0.99 million deaths and 50.7 million DALYs. Breast, tracheal, bronchus and lung (TBL), cervical, colon and stomach cancers were the leading causes of DALYs. The DALY rate for early-onset cancer excluding NMSC changed from 65.7 million in 2012 to 67.0 million in 2021, with an estimated annual percentage change (EAPC) of -0.49%. While the DALY rate plateaued for females, it decreased by -0.95% for males. Ten of 33 cancer groups exhibited an EAPC > 0. The high SDI quintile had 1,100 DALYs per 100,000 caused by early-onset cancers excluding NMSC, with the highest declining trend in DALY and mortality rates, while the high-middle SDI quintile had the highest early-onset mortality rates. Rising trends in cancer incidence and mortality were especially notable among females in the middle, low-middle, and low SDI quintiles.</p><p><strong>Conclusion: </strong>The global burden of early-onset cancer differs significantly by SDI quintile and gender. The increasing burden across multiple cancer groups poses a significant public health challenge. The rising burden of multiple cancer types is alarming, highlighting the need for increased policy support and targeted medical assistance to address the disparities in their impact.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"38"},"PeriodicalIF":9.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New exploration of KRAS<sup>G12D</sup> inhibitors and the mechanisms of resistance.","authors":"Ying Li, Junfeng Zhao, Yintao Li","doi":"10.1186/s40164-025-00637-4","DOIUrl":"10.1186/s40164-025-00637-4","url":null,"abstract":"<p><p>The development of Kirsten rat sarcoma viral oncogene homologue (KRAS) targeted therapies has been the focus of cancer treatment. The most common mutant subtypes of KRAS driver genes are G12C, G12V, and G12D, and are associated with poor prognosis. Up to now, inhibitors specifically targeting KRAS<sup>G12D</sup> mutant proteins are all in the pre-clinical/early clinical research stage, and there is still a lack of effective clinical targeting strategies. In their recently published article, Zhou et al. developed a high-affinity, selective, long-acting, non-covalent KRAS<sup>G12D</sup>-specific inhibitor and, further combined with the proteasome inhibitor carfilzomib, found that this protocol can achieve the purpose of killing mutant cell lines and inhibiting tumor growth in vitro and in vivo. Here, we aim to describe a potential novel therapy for patients with KRAS<sup>G12D</sup> mutations and present the first KRAS<sup>G12D</sup>-specific inhibitor to be proven as clinically effective. Different mutations of KRAS gene and mechanisms of KRAS drug resistance were also discussed.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"39"},"PeriodicalIF":9.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.","authors":"Qiongjie Hu, Yueli Shi, Huang Wang, Liuwen Bing, Zhiyong Xu","doi":"10.1186/s40164-025-00627-6","DOIUrl":"10.1186/s40164-025-00627-6","url":null,"abstract":"<p><p>Immunotherapy targeting immune checkpoints has gained traction across various cancer types in clinical settings due to its notable advantages. Despite this, the overall response rates among patients remain modest, alongside issues of drug resistance and adverse effects. Hence, there is a pressing need to enhance immune checkpoint blockade (ICB) therapies. Post-translational modifications (PTMs) are crucial for protein functionality. Recent research emphasizes their pivotal role in immune checkpoint regulation, directly impacting the expression and function of these key proteins. This review delves into the influence of significant PTMs-ubiquitination, phosphorylation, and glycosylation-on immune checkpoint signaling. By targeting these modifications, novel immunotherapeutic strategies have emerged, paving the way for advancements in optimizing immune checkpoint blockade therapies in the future.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"37"},"PeriodicalIF":9.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineered circular RNA-based DLL3-targeted CAR-T therapy for small cell lung cancer.","authors":"Jingsheng Cai, Zheng Liu, Shaoyi Chen, Jingwei Zhang, Haoran Li, Xun Wang, Feng Yang, Shaodong Wang, Xiao Li, Yun Li, Kezhong Chen, Jun Wang, Ming Sun, Mantang Qiu","doi":"10.1186/s40164-025-00625-8","DOIUrl":"10.1186/s40164-025-00625-8","url":null,"abstract":"<p><strong>Purpose: </strong>Circular RNA (circRNA) has emerged as a promising RNA therapeutic molecule due to its enhanced stability and prolonged protein expression compared to messenger RNA (mRNA). Using circRNA to construct transient Chimeric Antigen Receptor (CAR)-T cells can mitigate the limitations of conventional viral vector-based CAR-T approaches, such as complex process and long-term side effects.</p><p><strong>Methods: </strong>The study first reconfirmed the advantageous properties of circRNA, focusing on its stability and protein expression efficiency. Electroporation conditions were then optimized for the efficient delivery of circRNA into human primary T cells. Subsequently, a circRNA encoding the anti-Delta-like Ligand 3 (DLL3) CAR was constructed, and CAR-T cells were generated via electroporation. The efficacy of circRNA-based CAR-T cells was compared to mRNA-based CAR-T cells in both in vitro and in vivo models, including subcutaneous and orthotopic small cell lung cancer (SCLC) mouse models.</p><p><strong>Results: </strong>CircRNA-based CAR-T cells demonstrated superior efficacy against SCLC compared to mRNA-based CAR-T cells. In vitro experiments showed enhanced tumor-killing effects, while in vivo studies revealed complete elimination of human SCLC tumors in both subcutaneous and orthotopic mouse models. These results underscored the therapeutic advantages of circRNA in CAR-T cell therapy.</p><p><strong>Conclusions: </strong>This study validated the feasibility of the circRNA-electroporation strategy in CAR-T cell therapy and offered a potentially effective approach for treating SCLC, highlighting the potential of circRNA-based technologies in advancing cell therapies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"35"},"PeriodicalIF":9.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exosomal PD-L1 and lactate versus tissue PD-L1 as biomarkers for clinical outcomes of PD-1 Blockade plus chemotherapy in metastatic esophagogastric signet ring cell carcinoma.","authors":"Yuanyuan Tian, Wei Shi, Jing Wang, Wenjie Zhang, Lingling Xia, Lijuan Gao, Hu Qiu, Zhenhua Yu, Yongfeng Zhang, Yongshun Chen","doi":"10.1186/s40164-025-00615-w","DOIUrl":"10.1186/s40164-025-00615-w","url":null,"abstract":"<p><p>In this investigator-initiated, prospective, exploratory study, biomarkers predictive of clinical outcomes of first-line immune checkpoint inhibitor (ICI, nivolumab or pembrolizumab) plus XELOX(oxaliplatin and capecitabine) were identified in human epidermal growth factor receptor 2 (HER2)-negative patients with metastatic esophagogastric signet ring cell carcinoma. The findings showed an objective response rate (ORR) of 51.5% and a disease control rate of 86.8%, the median progression-free survival (PFS) for the entire cohort was 6.63 months. PD-L1 expression level in tumor tissues could not identify a high PD-L1 group that significantly benefited from ICI plus XELOX in terms of the ORR and PFS. By contrast, the patients expressing low exosomal PD-L1 or lactate in peripheral blood plasma before treatment initiation demonstrated a significantly increased ORR and prolonged PFS compared to that with high exosomal PD-L1 or lactate, patients with combining predictor of exosomal PD-L1 and lactate lower than - 0.249 was associated with a better ORR (82.1% vs. 30.0%, P < 0.001) and a longer median PFS (13.83 vs. 5.50 months, P < 0.001) compared to those with combining predictor ≥-0.249. The results also revealed that exosomal PD-L1 levels in peripheral blood plasma before the treatment were significantly correlated with the frequency of CD8<sup>+</sup> T cells (P = 0.007), and in patients after receiving ICI plus XELOX, high exosomal PD-L1 level was associated with more PD-1<sup>+</sup> Treg cells, high exosomal lactate level was associated with less CD8<sup>+</sup> T cells and more Treg cells. Thus, the levels of PD-L1 and lactate in exosomes may affect the balance between Treg cells and CD8<sup>+</sup>T cells, leading to treatment resistance to ICI plus XELOX. Compared to PD-L1 expression level in tumor tissues, exosomal PD-L1 and lactate levels could more accurately predict clinical outcomes of HER2-negative patients with metastatic esophagogastric signet ring cell carcinoma receiving first-line PD-1 blockade plus chemotherapy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"34"},"PeriodicalIF":9.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timothy Schieber, Kelly Brunk, Anna Clennon, Benjamin L Woolbright, Leonidas E Bantis, Dennis Grauer, Tiewei Cheng, Saqib Abbasi, Elizabeth Wulff-Burchfield, Rahul Parikh, Haoran Li
{"title":"Efficacy and safety of immune checkpoint inhibitors in metastatic penile squamous cell carcinoma: a retrospective multicenter analysis.","authors":"Timothy Schieber, Kelly Brunk, Anna Clennon, Benjamin L Woolbright, Leonidas E Bantis, Dennis Grauer, Tiewei Cheng, Saqib Abbasi, Elizabeth Wulff-Burchfield, Rahul Parikh, Haoran Li","doi":"10.1186/s40164-025-00629-4","DOIUrl":"10.1186/s40164-025-00629-4","url":null,"abstract":"<p><p>Penile squamous cell carcinoma (PSCC) is a rare malignancy, and first-line therapy typically involves cisplatin-based chemotherapy. However, these regimens are often unsuitable for patients with poor performance status or advanced age due to their toxicity. This retrospective, multicenter study evaluated patients with metastatic PSCC who received immune checkpoint inhibitor (ICI) therapy between 2017 and 2024. A total of 10 patients met the inclusion criteria. The median age was 75 years, and 50% had an ECOG performance status of 2 or higher. The objective response rate (ORR) was 30%, and the disease control rate (DCR) was 40%. The duration of response and disease control was over 12 months and 8 months respectively in all patients with response or disease control. The median progression-free survival (PFS) was 2.82 months, and the median overall survival (OS) was 4.32 months. PD-L1 and HPV-positive patients had a 67% response rate (n = 2/3). No patients experienced severe immune-related adverse events (irAEs). This multicenter retrospective analysis suggests that ICI monotherapy may be a promising treatment option for patients with advanced PSCC who are either ineligible for first-line platinum-based chemotherapy or who have progressed after platinum-based chemotherapy, including those with poor performance status. Further studies are needed to confirm these findings and identify baseline patient characteristics that may optimize selection criteria.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"36"},"PeriodicalIF":9.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meiying Luo, Xiaohuan Wang, Guoji Yu, Jing Ji, Long Li, Fan Song
{"title":"Development of a bispecific antibody-drug conjugate targeting EpCAM and CLDN3 for the treatment of multiple solid tumors.","authors":"Meiying Luo, Xiaohuan Wang, Guoji Yu, Jing Ji, Long Li, Fan Song","doi":"10.1186/s40164-025-00624-9","DOIUrl":"10.1186/s40164-025-00624-9","url":null,"abstract":"<p><p>Epithelial cell adhesion molecule (EpCAM), a tumor antigen for antibody-drug conjugates (ADCs), is highly expressed in many epithelial cancers. However, the clinical progress of EpCAM ADCs has been challenging, primarily due to their toxicity in normal high-expression tissues such as the gastrointestinal tract. CLDN3 is highly co-expressed with EpCAM in various human malignancies, coupled with its minimal presence in normal tissues, rendering it an ideal target for developing potent therapeutic ADCs. Here, we developed a bispecific ADC (BsADC) targeting EpCAM and CLDN3, designed to avoid toxicity in normal tissues with high EpCAM expression. The parental monoclonal antibodies (mAbs) were screened for high binding and endocytosis activities on tumor cell lines. We then modified them into monovalent structures and selected clones with decreased binding and endocytosis activities. We combined these clones into bispecific antibodies (BsAbs) and finally chose the molecules with restored binding and endocytosis activities as lead molecules. The BsADCs were generated by conjugating the Drutecan (Dxd) to BsAbs via a cleavable linker. These conjugates exhibit potent binding and effectively inhibit the growth of tumor cells with high levels of both EpCAM and CLDN3, indicating their anti-tumor efficacy. Importantly, they show weak binding to cells with high EpCAM but low CLDN3, implying minimal toxicity to normal tissues with elevated EpCAM expression. Moreover, the BsADCs displayed advantageous pharmacokinetics and low toxicity in mice. These findings position the BsADCs targeting EpCAM and CLDN3 as promising candidates for treating multiple solid tumors.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"33"},"PeriodicalIF":9.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lactylation modification in cancer: mechanisms, functions, and therapeutic strategies.","authors":"Mengqi Lv, Yefei Huang, Yansu Chen, Kun Ding","doi":"10.1186/s40164-025-00622-x","DOIUrl":"10.1186/s40164-025-00622-x","url":null,"abstract":"<p><p>Cancer remains the leading cause of mortality worldwide, and the emergence of drug resistance has made the identification of new therapeutic targets imperative. Lactate, traditionally viewed as a byproduct of glycolysis with limited ATP-producing capacity, has recently gained recognition as a critical signaling molecule. It plays a key role not only in cancer cell metabolism but also in shaping the tumor microenvironment (TME). Histone lysine lactylation, a newly identified post-translational modification, has been shown to influence a range of cellular processes in cancer. Current research focuses on the mechanisms and functions of histone lactylation in cancer, including its role in gene expression regulation, signal transduction, and protein synthesis. However, despite these advancements, there are still plenty of barriers in the quest to unravel the mechanisms of lactylation modification. The emergence of single-cell and spatial transcriptomics may offer valuable insights for selecting targets. This review provides a comprehensive summary of the mechanisms and the applications of lactylation modification in clinical settings. Through a detailed analysis, we identify the key challenges and limitations that exist in the current research landscape. These insights lay the groundwork for future studies by highlighting promising research directions.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"32"},"PeriodicalIF":9.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}