OncoTargets and therapy最新文献

{"title":"Ubiquitination-Binding Enzyme 2C is Associated with Cancer Development and Prognosis and is a Potential Therapeutic Target.","authors":"Mengjie Zhao, Jielong Li, Rui Wang, Lida Mi, Yan Gu, Rongjin Chen, Yangyang Li, Woda Shi, Yajun Zhang","doi":"10.2147/OTT.S485053","DOIUrl":"10.2147/OTT.S485053","url":null,"abstract":"<p><p>UBE2C (Ubiquitination-binding enzyme 2C), one of the E2 enzymes encoded in the human genome, is a component of the ubiquitin proteasome system and plays a pivotal role in regulating cell cycle progression. Moreover, UBE2C is highly expressed and may play a pivotal role in both high-incidence and high-mortality malignancies, including lung cancers, breast cancers, and esophageal cancers. UBE2C influences a number of key processes, including cell cycle progression, tumor invasion and metastasis, proliferation, and drug resistance. However, few articles have systematically summarized the role of UBE2C in cancer. The aim of this review is to describe the structure and function of UBE2C, focusing on the current status of UBE2C research in malignant tumors. Furthermore, this review presents the potential of UBE2C as a new therapeutic target and a diagnostic and prognostic biomarker. Finally, future research directions for UBE2C are proposed. It is of great value to explore the mechanism of action of UBE2C in the tumor microenvironment (TME). A comprehensive and coherent comprehension of UBE2C will undoubtedly facilitate its transition from fundamental research to clinical applications.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1159-1171"},"PeriodicalIF":2.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Non Coding RNA SNHG16 Facilitates Proliferation, Migration, Invasion and Autophagy of Neuroblastoma Cells via Sponging miR-542-3p and Upregulating ATG5 Expression [Retraction].","authors":"","doi":"10.2147/OTT.S509994","DOIUrl":"https://doi.org/10.2147/OTT.S509994","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/OTT.S226915.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1157-1158"},"PeriodicalIF":2.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Neoadjuvant Immunotherapy Combined with Sandwich Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma: A Retrospective Study.","authors":"Huimin Fu, Zetan Chen, Jiawei Chen, Shuai Zhang","doi":"10.2147/OTT.S489714","DOIUrl":"10.2147/OTT.S489714","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to determine the safety and feasibility of neoadjuvant immunotherapy combined with sandwich chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC).</p><p><strong>Patients and methods: </strong>This retrospective study involved 37 patients with locally advanced NPC treated with the above regimen. All patients received four cycles of neoadjuvant immunotherapy and chemotherapy at three-week intervals, including the administration of PD-1 inhibitors, namely, sintilimab (a fixed dose of 200 mg on Day 1) or toripalimab (240 mg on Day 1). The chemotherapy program consisted of nab-paclitaxel (260 mg/m2, Day 1) plus nedaplatin (85 mg/m2, Day 1). Concurrent with intensity-modulated radiation therapy (IMRT), the patients received targeted drug therapy with nimotuzumab (200 mg) across six cycles. Finally, 4 cycles of S-1 adjuvant chemotherapy were administered.</p><p><strong>Results: </strong>In this study, the efficiency of neoadjuvant immunotherapy combined with chemotherapy was 94.6%, the CR rate was 67.6%, and the efficiency 3 months after IMRT was 100%. The 2-year overall survival (OS), locoregional control (LCR), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates of the whole group were 97.3%, 94.6%, 97.3% and 91.9%, respectively. Neutropenia was the most common hematological toxicity (100%), and the incidence of grade ≥ 3 neutropenia was 40.5%. Grade 3 anemia and thrombocytopenia did not occur. Additionally, no adverse reactions, such as hypothyroidism, immune pneumonia, or myocarditis, occurred in the whole group. However, the incidences of rash, musculoskeletal pain, and hepatotoxicity were high (45.9%, 54.1% and 37.8%, respectively).</p><p><strong>Conclusion: </strong>The survival benefit of neoadjuvant immunotherapy combined with sandwich chemoradiotherapy is excellent, with tolerable toxicity, in patients with locally advanced NPC. This study provides new insight into the application of immunotherapy in locally advanced NPC.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1145-1155"},"PeriodicalIF":2.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case Report of Envafolimab in the Treatment of Microsatellite Stable (MSS) Metastatic Colon Cancer.","authors":"Yunshan Yang, Xu Luo, Li Dai, Tong He, Siqi Luo, Yongjin Zhou, Haibin Wang, Zhiqiang Yan, Qian Wang, Xiangren Jin","doi":"10.2147/OTT.S473040","DOIUrl":"https://doi.org/10.2147/OTT.S473040","url":null,"abstract":"<p><p>Envafolimab is a novel inhibitor for programmed cell death protein-ligand 1 (PD-L1) that can be administered subcutaneously. It has been found to be effective and safe in the treatment of advanced high microsatellite unstable (MSI-H) / mismatch repair deficient (dMMR) solid tumors. Currently, the efficacy of programmed cell death protein-1 (PD-1) / programmed cell death protein-ligand 1 (PD-L1) inhibitors in the treatment of microsatellite stable (MSS) tumors is not clear. We report a case of advanced colon cancer with MSS metastases in bilateral clavicle, mediastinum, retroperitoneum, bilateral hilum, and left side of thoracic 11/12 vertebral body. After 8 months of Envafolimab treatment, there was a significant reduction in metastatic lesions. As of February 1st, 2024, the patient exhibited no significant adverse reactions. The current efficacy evaluation was the partial response (PR), and the overall survival (OS) was more than 12 months. Considering the safety and efficacy of Envafolimab observed in our case, we believe that Envafolimab may be a promising drug for the treatment of MSS metastatic colon cancer.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1137-1144"},"PeriodicalIF":2.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Lymphovascular Infiltration and Tumor-Associated Macrophages in Cervical Cancer Immunoescape.","authors":"Liming Guan, Xuexiang Xu, Junhao Xu, Gang Xu, Yunzhu Zhang, Haitao Xia","doi":"10.2147/OTT.S468484","DOIUrl":"10.2147/OTT.S468484","url":null,"abstract":"<p><strong>Background: </strong>Exact detection of lymphovascular infiltration (LVI) status can guide accurate surgical operation scope in cervical cancer, but LVI reduces the overall survival (OS) of patients and is not easily detected by hematoxylin-eosin (H&E) staining. The role of tumor-associated macrophages (TAMs) in this process is not well defined.</p><p><strong>Methods: </strong>Early-stage cervical cancer patients received carbon nanoparticles for sentinel lymph-node mapping, laparotomy pelvic lymph-node dissection, and radical hysterectomy. The excised specimens were analyzed using ultrastaging, double immunohistochemical (IHC) staining, flow cytometry, and Western blot analysis. Single-cell data from the Gene Expression Omnibus for cervical cancer were obtained and analyzed.</p><p><strong>Results: </strong>The integration of carbon nanoparticle mapping, ultrastaging, and double IHC staining enhanced the detection of tumor LVI over H&E staining (41.8% [41/98] vs. 20.4% [20/98], <i>P</i>=0.046). When the number of vascular invasion foci was greater than two, there was a negative correlation with OS (<i>P</i><0.05). More M2 TAMs emerged surrounding the tumor vasculature labeled by double IHC staining, accompanied by a higher M2:M1 ratio detected with flow cytometry (<i>P</i><0.05). M2 TAM numbers were positively correlation with the degree of tumor LVI (<i>P</i>=0.0024), combined with higher protein expression of MMP2, SPARC, and GNLY in the tumor LVI-positive group on Western blot analysis, and the OS of the patients decreased accordingly. Single-cell data showed that the M1:M2 ratio decreased significantly, accompanied by higher M2 TAM-related gene expression. Immunosurveillance and anti-immunoescape scores for M1 were obviously higher than for M2 TAMs. GO and KEGG analysis showed M2 TAM activity increased from precancerous lesions to cervical cancer.</p><p><strong>Conclusion: </strong>Combining different methods may accurately determine tumor LVI status, guide exact surgical operation scope, and improve cervical cancer patient outcomes. M2 TAM activity increased in cervical cancer, forming an immunosuppressive environment, TAM-related genes could be good markers in determining cervical cancer LVI and serve as potential targets for immunotherapy.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1117-1136"},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the Treatment of Rare Mutations in Non-Small Cell Lung Cancer.","authors":"Yanning Sun, Li Ma, Xiaofei Zhang, Zhaoxia Wang","doi":"10.2147/OTT.S487870","DOIUrl":"10.2147/OTT.S487870","url":null,"abstract":"<p><p>Lung cancer is a malignant tumor with the highest morbidity and mortality rate worldwide, with nearly 2.5 million new cases and more than 1.8 million deaths reported globally in 2022. Lung cancer is broadly categorized into two main types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC accounting for about 85% of all cases. Early-stage lung cancers often present without obvious symptoms, resulting in most patients being diagnosed at an advanced stage where traditional chemotherapy has limited efficacy. Recent advances in molecular biology have elucidated the pivotal role of gene mutations in tumor development, paving the way for targeted therapies that have markedly benefited patients. Beyond the well-known epidermal growth factor receptor (EGFR) mutation, an increasing number of new molecular targets have been identified, including ROS1 rearrangement, BRAF mutation, NTRK fusion, RET fusion, MET mutation, KRAS G12C mutation, HER2 mutation, ALK rearrangement, and NRG1 fusion. Some of these targeted therapies have already been approved by the Food and Drug Administration (FDA), and many others are currently undergoing clinical trials. This review summarizes recent advances in NSCLC treatment with molecular targets, highlighting progress, challenges, and their impact on patient prognosis.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1095-1115"},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concentrations of Irinotecan and SN-38 in the Ascites and the Fluid Product of Cell-Free and Concentrated Ascites Reinfusion Therapy 9 Days After Administration of Irinotecan in a Patient with Gastric Cancer: A Case Report.","authors":"Keisuke Baba, Tomoki Tanie, Yasuo Matsubara, Yoshihiro Hirata, Hiroaki Ikematsu, Chiyo K Imamura, Narikazu Boku","doi":"10.2147/OTT.S486272","DOIUrl":"10.2147/OTT.S486272","url":null,"abstract":"<p><strong>Introduction: </strong>Cell-free and concentrated ascites reinfusion therapy (CART) is frequently used to relieve the symptoms caused by massive ascites due to peritoneal metastasis of gastric cancer, especially in the later stages of its clinical course. Irinotecan (CPT-11) is recommended for third- or later-line chemotherapy according to gastric cancer treatment guidelines. However, the concentrations of anti-cancer drugs in the ascites and the product of CART are not well known, it is considered that some amounts of anti-cancer drugs contained in the product of CART may be readministered and induce severe adverse reactions.</p><p><strong>Case presentation: </strong>A 66-year-old female with gastric cancer and massive ascites received third-line chemotherapy with CPT-11 (150 mg/m²) and ramucirumab (8 mg/kg). On day 7, the laboratory test showed a white blood cell count of 1,290/µL and neutrophil count of 480/µL. On day 9, the patient underwent CART, and the concentrations of CPT-11 and its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) were 1.18 ng/mL and 0.22 ng/mL in plasma, 0.95 ng/mL and 0.82 ng/mL in ascites, and 0.20 ng/mL and 0.17 ng/mL in the product of CART, respectively.</p><p><strong>Conclusion: </strong>Concentrations of CPT-11 and SN-38 remaining in ascites and the product of CART were low in an advanced gastric cancer patient 9 days after administration of CPT-11.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1089-1094"},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Cuproptosis-Related Genes for Molecular Subtyping: Predicting Prognostic and Therapeutic Response in Glioma.","authors":"Xiaochun Xia, Xiaoying Huang, Longxiang Wu, Pengqin Xu, Peng Li","doi":"10.2147/OTT.S481443","DOIUrl":"10.2147/OTT.S481443","url":null,"abstract":"<p><strong>Background: </strong>Cuproptosis, a metal-ion-dependent form of regulated cell death induced by copper overload, is emerging as a potential mechanism in high-grade glioma (HGG). Despite its significance, the role of cuproptosis in predicting the prognostic and therapeutic response in HGG remains poorly understood.</p><p><strong>Methods: </strong>We performed unsupervised clustering to stratify patients with HGG in the Chinese Glioma Genome Atlas (CGGA) according to the expression of 14 cuproptosis-related genes (CRGs) and validated in The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to explore the biological processes and pathways involved within distinct groups. We constructed the CupScore model to predict the responsiveness to immune checkpoint inhibitors (ICIs) therapy and chemotherapy in patients with HGG. Additionally, in vivo and in vitro experiments were performed to investigate the potential biological function of CDKN2A in HGG.</p><p><strong>Results: </strong>We identified two cuproptosis-related molecular subgroups with significantly different survival probabilities. Patients with HGG in cluster 1 were characterized as immune-desert phenotype with higher CupScore and lower expression of MHC complex, interferons, chemokines, interleukins, and immune checkpoints. In contrast, cluster 2 showed an immune-inflamed signature. We screened PI-103 as the most promising candidate for patients with higher CupScore and confirmed its experimental evidence and clinical trial status. Patients with lower CupScore showed higher response rates to anti-PD-L1 and anti-PD1 combined with anti-CTLA4 ICI therapy. Furthermore, in vivo and in vitro experiments revealed that CDKN2A enhanced the malignant phenotype of HGG.</p><p><strong>Conclusion: </strong>Cuproptosis has the ability to reprogram the tumor microenvironment (TME) in HGG, leading to the stratification of patients into two distinct molecular subgroups. The CupScore model emerged as a robust metric for predicting the prognostic and therapeutic benefits, as well as may therefore facilitate personalized treatment strategies for patients with HGG.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1069-1088"},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Four Cases with FUS/CHOP Fusion Gene Products Positive Myxoid Liposarcoma Responding Effectively to Trabectedin Monotherapy.","authors":"Hirohito Kirishi, Hiromichi Yamane, Nobuaki Ochi, Yusuke Sunada, Ayaka Mimura, Yoko Kosaka, Naruhiko Ichiyama, Tatsuyuki Kawahara, Yasunari Nagasaki, Hidekazu Nakanishi, Toshiyuki Kunisada, Nagio Takigawa","doi":"10.2147/OTT.S486163","DOIUrl":"10.2147/OTT.S486163","url":null,"abstract":"<p><strong>Background: </strong>Myxoid liposarcoma, a rare type of tumor, accounts for approximately 30% of all liposarcomas. Myxoid liposarcomas harboring the FUS/CHOP fusion gene have shown promising results with trabectedin in basic research and some clinical experiments. However, the efficacy and safety of trabectedin in chemotherapy-naive soft tissue sarcomas or FUS/CHOP fusion gene-positive myxoid liposarcomas have not yet been established. Therefore, we evaluated the effectiveness and safety of trabectedin monotherapy in four cases of myxoid liposarcoma harboring the FUS/CHOP fusion gene at our hospital.</p><p><strong>Patients and methods: </strong>We analyzed four patients with metastatic myxoid liposarcoma who underwent surgery at Okayama University and received chemotherapy at Kawasaki Medical School. These patients had positive test results for the FUS/CHOP fusion gene as an aid to pathological diagnosis by RT-PCR. RNA was extracted from tumor tissue sliced from frozen tumor specimens. Following reverse transcription, PCR was performed using TLS/FUS-CHOP primers. The resulting products were electrophoresed, and then the nucleotide sequences were confirmed.</p><p><strong>Case presentation: </strong>Case 1: A 44-year-old male started trabectedin as second-line therapy after initial chemotherapy, which included doxorubicin. To date, he has completed 9 cycles, showing a response for 6 months. Case 2: A 71-year-old male, deemed intolerant to doxorubicin, started trabectedin as his first-line treatment. He has undergone 50 cycles to date, maintaining a response for 56 months. Case 3: A 59-year-old female began trabectedin as second-line therapy after initial chemotherapy, including doxorubicin. She responded for 6 months before experiencing disease progression. Case 4: A 79-year-old male developed new lesions after one course of initial chemotherapy, including doxorubicin. He then began trabectedin and has maintained a response for 10 months to date.</p><p><strong>Conclusion: </strong>Compared to other chemotherapies, trabectedin demonstrated potentially higher efficacy and a favorable safety profile for patients with myxoid liposarcoma harboring the FUS/CHOP fusion gene.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1059-1067"},"PeriodicalIF":2.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential Treatment Options and Combination Strategies of KRAS-Mutated Lung Cancer.","authors":"Xinchao Zhao, Yawen Zheng, Yufeng Wang, Mingyan Zhang, Zhilin Dong, Yanan Liu, Meili Sun","doi":"10.2147/OTT.S484209","DOIUrl":"10.2147/OTT.S484209","url":null,"abstract":"<p><p>In non-small cell lung cancer (NSCLC), Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in up to 30% of all cases, with the most prevalent mutations occurring in codons 12 and 13. The development of <i>KRAS</i>-targeted drugs like sotorasib and adagrasib has generated significant excitement in the clinical arena, offering new therapeutic options. Their potential for combination with other treatments broadens the scope for clinical exploration. Acquired resistance to <i>KRAS exon 2 p.G12C</i> inhibitors is a significant challenge, with several reported mechanisms. In this scenario, combination therapy strategies that include targeting Src Homology Region 2 Domain-Containing Phosphatase-2 (SHP2), Son of Sevenless Homolog 1 (SOS1), or downstream effectors of <i>KRAS exon 2 p.G12C</i> are showing promise in overcoming such resistance. However, the efficacy of immune checkpoint inhibitors in this context still requires comprehensive evaluation. The response to anti-Programmed Cell Death Protein 1/Programmed Cell Death Protein 1 Ligand (anti-PD-1/PD-L1) drugs in NSCLC may be significantly influenced by co-occurring mutations, underscoring the need for a personalized approach to treatment based on the specific genetic profile of each tumor.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"1041-1057"},"PeriodicalIF":2.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}