Cancer Research and Treatment

Original Articles

Breast cancer

Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions: Bárbara Jaime dos Santos, Débora Balabram, Virginia Mara Reis Gomes, Carolina Costa Café de Castro, Paulo Henrique Costa Diniz, Marcelo Araújo Buzelin, Cristiana Buzelin Nunes; Cancer Res Treat. 2024;56(1):178-190. Published online August 1, 2023; DOI: https://doi.org/10.4143/crt.2023.386

Abstract PDF PubReader ePub: Purpose
Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients’ overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS.
Materials and Methods
IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS.
Results
Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B–like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor–positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS.
Conclusion
NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.

3,170 View
212 Download

FOXO1 Suppression is a Determinant of Acquired Lapatinib-Resistance in HER2-Positive Gastric Cancer Cells Through MET Upregulation: Jinju Park, Yiseul Choi, Young San Ko, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Min A Kim, Jae-Seon Lee, Mee Soo Chang, Jong-Wan Park, Byung Lan Lee; Cancer Res Treat. 2018;50(1):239-254. Published online March 24, 2017; DOI: https://doi.org/10.4143/crt.2016.580

Abstract PDF PubReader ePub

Purpose
Lapatinib is a candidate drug for treatment of trastuzumab-resistant, human epidermal growth factor receptor 2 (HER2)–positive gastric cancer (GC). Unfortunately, lapatinib resistance renders this drug ineffective. The present study investigated the implication of forkhead box O1 (FOXO1) signaling in the acquired lapatinib resistance in HER2-positive GC cells.
Materials and Methods
Lapatinib-resistant GC cell lines (SNU-216 LR2-8) were generated in vitro by chronic exposure of lapatinib-sensitive, HER2-positive SNU-216 cells to lapatinib. SNU-216 LR cells with FOXO1 overexpression were generated by stable transfection of a constitutively active FOXO1 mutant (FOXO1A3). HER2 and MET in SNU-216 LR cells were downregulated using RNA interference. The sensitivity of GC cells to lapatinib and/or cisplatin was determined by crystal violet assay. In addition, Western blot analysis, luciferase reporter assay and reverse transcription–polymerase chain reaction were performed.
Results
SNU-216 LR cells showed upregulations of HER2 and MET, but downregulation of FOXO1 compared to parental SNU-216 cells. FOXO1 overexpression in SNU-216 LR cells significantly suppressed resistance to lapatinib and/or cisplatin. In addition, FOXO1 negatively controlled HER2 and MET at the transcriptional level and was negatively controlled by these molecules at the post-transcriptional level. A positive crosstalk was shown between HER2 and MET, each of which increased resistance to lapatinib and/or cisplatin.
Conclusion
FOXO1 serves as an important linker between HER2 and MET signaling pathways through negative crosstalks and is a key regulator of the acquired lapatinib resistance in HER2-positive GC cells. These findings provide a rationale for establishing a novel treatment strategy to overcome lapatinib resistance in a subtype of GC patients.

Citations

Citations to this article as recorded by

The FOXO1/G6PC axis promotes gastric cancer progression and mediates 5‐fluorouracil resistance by targeting the PI3K/AKT/mTOR signaling pathway
Anna Han, Taorui Liu, Pan Du, Mengying Wang, Jiajing Liu, Liyan Chen
Molecular Carcinogenesis.2024; 63(4): 688. CrossRef
Characterization of MET Alterations in 37 Gastroesophageal Cancer Cell Lines for MET-Targeted Therapy
Jin-Soo Kim, Mi Young Kim, Sungyoul Hong
International Journal of Molecular Sciences.2024; 25(11): 5975. CrossRef
HER2-targeted therapies beyond breast cancer — an update
Jeesun Yoon, Do-Youn Oh
Nature Reviews Clinical Oncology.2024; 21(9): 675. CrossRef
Resistance to Anti-HER2 Therapies in Gastrointestinal Malignancies
Christiana Mo, Michelle Sterpi, Hyein Jeon, Fernand Bteich
Cancers.2024; 16(16): 2854. CrossRef
The novel BCL-2/BCL-XL inhibitor APG-1252-mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer
Qiu-yun Luo, Jing Yang, Tian Di, Zeng-fei Xia, Lin Zhang, Wen-tao Pan, Shan Shi, Li-qiong Yang, Jian Sun, Miao-zhen Qiu, Da-jun Yang
Acta Pharmacologica Sinica.2024;[Epub] CrossRef
FoxO1 Deficiency in Monocytic Myeloid‐Derived Suppressor Cells Exacerbates B Cell Dysfunction in Systemic Lupus Erythematosus
Liping Tan, Wei Kong, Kangxing Zhou, Shuangan Wang, Jun Liang, Yayi Hou, Huan Dou
Arthritis & Rheumatology.2024;[Epub] CrossRef
Targeted and Immunotherapy Approaches in HER2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma: A New Era
Maluki Radford, Hassan Abushukair, Stijn Hentzen, Ludimila Cavalcante, Anwaar Saeed
Journal of Immunotherapy and Precision Oncology.2023; 6(3): 150. CrossRef
Resistance mechanisms to HER2-targeted therapy in gastroesophageal adenocarcinoma: A systematic review
Dionne Blangé, Charlotte I. Stroes, Sarah Derks, Maarten F. Bijlsma, Hanneke W.M. van Laarhoven
Cancer Treatment Reviews.2022; 108: 102418. CrossRef
The FOXO family of transcription factors: key molecular players in gastric cancer
Ying Liu, Xiang Ao, Yi Jia, Xiaoge Li, Yu Wang, Jianxun Wang
Journal of Molecular Medicine.2022; 100(7): 997. CrossRef
VGLL1 phosphorylation and activation promotes gastric cancer malignancy via TGF-β/ERK/RSK2 signaling
Joo-Young Im, Da-Mi Kim, Hyunkyung Park, Mi-Jung Kang, Da-Yoon Kim, Kwan Young Chang, Bo-Kyung Kim, Misun Won
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2021; 1868(1): 118892. CrossRef
The efficacy and safety of onartuzumab in patients with solid cancers: A meta-analysis of randomized trials
BumJun Kim, Dalyong Kim, JungHan Kim, HyeongSu Kim, HyunJoo Jang
Indian Journal of Cancer.2021; 58(2): 232. CrossRef
HER2-targeted therapies in gastric cancer
Yinxing Zhu, Xuedan Zhu, Xiaowei Wei, Cuiju Tang, Wenwen Zhang
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2021; 1876(1): 188549. CrossRef
Current therapeutic options for gastric adenocarcinoma
C.R. Akshatha, Smitha Bhat, R. Sindhu, Dharini Shashank, Sarana Rose Sommano, Wanaporn Tapingkae, Ratchadawan Cheewangkoon, Shashanka K. Prasad
Saudi Journal of Biological Sciences.2021; 28(9): 5371. CrossRef
Diverse roles of FOXO family members in gastric cancer
Yu-Han Chen, Chun-Lan Li, Wen-Jia Chen, Jing Liu, Hua-Tao Wu
World Journal of Gastrointestinal Oncology.2021; 13(10): 1367. CrossRef
Overcoming resistance to targeted therapy using MET inhibitors in solid cancers: evidence from preclinical and clinical studies
Nehad M. Ayoub, Dalia R. Ibrahim, Amer E. Alkhalifa
Medical Oncology.2021;[Epub] CrossRef
Caveolin-1 Promotes Chemoresistance of Gastric Cancer Cells to Cisplatin by Activating WNT/β-Catenin Pathway
Xi Wang, Bin Lu, Chunyan Dai, Yufei Fu, Ke Hao, Bing Zhao, Zhe Chen, Li Fu
Frontiers in Oncology.2020;[Epub] CrossRef
Machine Learning-Guided Prediction of Antigen-Reactive In Silico Clonotypes Based on Changes in Clonal Abundance through Bio-Panning
Duck Kyun Yoo, Seung Ryul Lee, Yushin Jung, Haejun Han, Hwa Kyoung Lee, Jerome Han, Soohyun Kim, Jisu Chae, Taehoon Ryu, Junho Chung
Biomolecules.2020; 10(3): 421. CrossRef
FOXO transcription factor family in cancer and metastasis
Yannasittha Jiramongkol, Eric W.-F. Lam
Cancer and Metastasis Reviews.2020; 39(3): 681. CrossRef
In vitro and in vivo Anti-Tumor Effects of Pan-HER Inhibitor Varlitinib on Cholangiocarcinoma Cell Lines

Hasaya Dokduang, Wassana Jamnongkarn, Bundit Promraksa, Manida Suksawat, Sureerat Padthaisong, Malinee Thanee, Jutarop Phetcharaburanin, Nisana Namwat, Sakkarn Sangkhamanon, Attapol Titapun, Narong Khuntikeo, Poramate Klanrit, Watcharin Loilome
Drug Design, Development and Therapy.2020; Volume 14: 2319. CrossRef
MiR-27a promotes EMT in ovarian cancer through active Wnt/
Li-Ya Zhang, Yuan Chen, Jue Jia, Xi Zhu, Yan He, Li-Ming Wu
Cancer Biomarkers.2019; 24(1): 31. CrossRef
Role of FoxO Proteins in Cellular Response to Antitumor Agents
Giovanni Luca Beretta, Cristina Corno, Nadia Zaffaroni, Paola Perego
Cancers.2019; 11(1): 90. CrossRef
Members of FOX family could be drug targets of cancers
Jinhua Wang, Wan Li, Ying Zhao, De Kang, Weiqi Fu, Xiangjin Zheng, Xiaocong Pang, Guanhua Du
Pharmacology & Therapeutics.2018; 181: 183. CrossRef
FoxO-1 contributes to the efficacy of the combination of the XPO1 inhibitor selinexor and cisplatin in ovarian carcinoma preclinical models
Cristina Corno, Simone Stucchi, Michelandrea De Cesare, Nives Carenini, Serena Stamatakos, Emilio Ciusani, Lucia Minoli, Eugenio Scanziani, Christian Argueta, Yosef Landesman, Nadia Zaffaroni, Laura Gatti, Paola Perego
Biochemical Pharmacology.2018; 147: 93. CrossRef
Nuclear division cycle 80 promotes malignant progression and predicts clinical outcome in colorectal cancer
Xuebing Yan, Linsheng Huang, Liguo Liu, Huanlong Qin, Zhenshun Song
Cancer Medicine.2018;[Epub] CrossRef
Systems analysis of key genes and pathways in the progression of hepatocellular carcinoma
Yu-Kui Shang, Fanni Li, Yi Zhang, Ze-Kun Liu, Zi-Ling Wang, Huijie Bian, Zhi-Nan Chen
Medicine.2018; 97(23): e10892. CrossRef
The Dominant Role of Forkhead Box Proteins in Cancer
Duc-Hiep Bach, Nguyen Phuoc Long, Thi-Thu-Trang Luu, Nguyen Hoang Anh, Sung Won Kwon, Sang Kook Lee
International Journal of Molecular Sciences.2018; 19(10): 3279. CrossRef
HSP90 inhibitor, AUY922, debilitates intrinsic and acquired lapatinib-resistant HER2-positive gastric cancer cells
Kang-Seo Park, Yong Sang Hong, Junyoung Choi, Shinkyo Yoon, Jihoon Kang, Deokhoon Kim, Kang-Pa Lee, Hyeon-Su Im, Chang Hoon Lee, Seyoung Seo, Sang-We Kim, Dae Ho Lee, Sook Ryun Park
BMB Reports.2018; 51(12): 660. CrossRef
FOXO1 reduces tumorsphere formation capacity and has crosstalk with LGR5 signaling in gastric cancer cells
Yiseul Choi, Jinju Park, Young San Ko, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Min A Kim, Jae-Seon Lee, Mee Soo Chang, Byung Lan Lee
Biochemical and Biophysical Research Communication.2017; 493(3): 1349. CrossRef
Trifluoperazine Activates FOXO1-Related Signals to Inhibit Tumor Growth in Hepatocellular Carcinoma
Jingwen Jiang, Zhongxi Huang, Xuewu Chen, Rongcheng Luo, Hongbin Cai, Hairu Wang, Hui Zhang, Tao Sun, Yunfang Zhang
DNA and Cell Biology.2017; 36(10): 813. CrossRef

11,904 View
387 Download
29 Web of Science
29 Crossref

First
Prev
Page of 1
Next
Last

Search