Cancer Research and Treatment

Original Articles

Combination of Niraparib and Lapatinib for Ovarian Cancer Treatment: Feiyun Jiang, Xingyu Liu, Yalan Wei, Yeping Ding, Wen Cai, Shanshan Xu, Bin Tang; Received May 6, 2025 Accepted July 28, 2025 Published online July 29, 2025; DOI: https://doi.org/10.4143/crt.2025.553 [Epub ahead of print]

Purpose
Ovarian cancer is characterized by high malignancy, frequent recurrence with drug resistance, and poor 5-year survival rates. Although poly(ADP-ribose) polymerase (PARP) inhibitors like niraparib show efficacy in homologous recombination repair-deficient ovarian cancer, resistance often develops. This study aimed to evaluate the synergistic therapeutic potential of combining the epidermal growth factor receptor (EGFR) inhibitor lapatinib and the PARP inhibitor niraparib to evaluate combinatorial effects and enhance antitumor effects in ovarian cancer.
Materials and Methods
Lapatinib (EGFR inhibitor) and niraparib (PARP inhibitor) were screened from the U.S. Food and Drug Administration/China Food and Drug Administration–approved drug library. In vitro assays assessed ovarian cancer cell proliferation, clonogenicity, metastatic ability, and apoptosis. Mechanistic studies analyzed phosphorylation levels of EGFR, AKT, and ERK via biochemical assays. In vivo experiments were conducted to validate the antitumor efficacy of the drug combination.
Results
The lapatinib-niraparib combination synergistically suppressed ovarian cancer cell proliferation, inhibited clonogenic formation and metastasis, and induced apoptosis. Mechanistically, the dual therapy reduced phosphorylation of EGFR, AKT, and ERK, indicating suppression of downstream signaling pathways. Both in vitro and in vivo experiments demonstrated significant inhibition of ovarian cancer growth with the combination treatment.
Conclusion
EGFR/human epidermal growth factor receptor 2–expressing ovarian cancer cells responded to lapatinib and that a synergistic effect was observed when combined with niraparib. These findings highlight its promising clinical potential for improving outcomes in ovarian cancer patients.

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Single versus dual EGFR/PARP inhibition: Mechanistic rationale, synthetic approaches, pharmacophoric features, structure–activity relationships, and therapeutic perspectives
Eman M. Elkafoury, Tarek F. El-Moselhy, Mervat H. El-Hamamsy, Eman A. El-Bastawissy, Esraa Y. Rabea, Kamyar Afarinkia, Peter A. Sidhom
European Journal of Medicinal Chemistry.2026; 316: 119047. CrossRef

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Lung and Thoracic cancer

A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer: Eo Jin Kim, Yong-Hee Cho, Dong Ha Kim, Dae-Hyun Ko, Eun-Ju Do, Sang-Yeob Kim, Yong Man Kim, Jae Seob Jung, Yoonmi Kang, Wonjun Ji, Myeong Geun Choi, Jae Cheol Lee, Jin Kyung Rho, Chang-Min Choi; Cancer Res Treat. 2022;54(4):1005-1016. Published online December 3, 2021; DOI: https://doi.org/10.4143/crt.2021.986

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.
Materials and Methods
Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×10⁹ or 4×10⁹ cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life.
Results
Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×10⁹ cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001).
Conclusion
Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

Citations

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Cell therapy in sarcoma: current landscape and future directions
Taha Koray Sahin, Theodora Germetaki, Deniz Can Guven, Serkan Akin, Omer Dizdar, Fiona Thistlethwaite, Elizabeth A Connolly, Kok Haw Jonathan Lim
Journal for ImmunoTherapy of Cancer.2026; 14(1): e013396. CrossRef
NK cell infusion is well-tolerated and shows preliminary efficacy in patients with recurrent hepatocellular carcinoma post-liver transplantation : a phase I trial
Fan Yang, Yihang Gong, Xiaofang Zheng, Beibei Ni, Jianxi Lu, Xiaoyan Chen, Jintao Cheng, Panlong Li, Cong Du, Yunhao Chen, Yingcai Zhang, Shuhong Yi, Guoying Wang, Qi Zhang, Yang Yang, Wenjie Chen
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Lucie Biard, Vincent Lévy, Sylvie Chevret, Annette Künkele, Stefanie Grunwald, Alessandro Aiuti, Bjarne Kuno Møller, Reno Debets, Stephan Mielke, Johan van Eldere, Antonia Müller, Silvia Martin Lluesma, Lorena Consolino, Matt Bolz-Johnson, Stefano Benvenu
Molecular Therapy Advances.2026; 34(1): 201651. CrossRef
Human natural killer cells exhibit potent antifungal activity against azole-resistant Aspergillus fumigatus and diverse filamentous fungi
Hotaka Namie, Takahiro Takazono, Satoshi Irifune, Satoru Koga, Yuya Ito, Nana Nakada, Tatsuro Hirayama, Masataka Yoshida, Kazuaki Takeda, Shotaro Ide, Naoki Iwanaga, Masato Tashiro, Naoki Hosogaya, Noriho Sakamoto, Haruki Okamura, Yoshimasa Tanaka, Katsun
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Cellular Therapies in Solid Tumors: Are We Ready for Primetime?
Giuseppe Maiocco, Vinicius Ernani, Michael P. Gustafson, Salman R. Punekar, Konstantinos Leventakos, Julian Molina, Yousef Zakharia, Mitesh Borad, Antonious Z. Hazim
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Adopting tomorrow’s therapies today: a perspective review of adoptive cell therapy in lung cancer
Faith Abodunrin, Daniel J Olson, Oluwatosin Emehinola, Christine M Bestvina
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Preclinical investigation of anti-tumor efficacy of allogeneic natural killer cells combined with cetuximab for head and neck squamous cell carcinoma
Chaeyeon Kim, Mina Han, Gamin Kim, Wonrak Son, Jeongah Kim, Minchan Gil, Yong-Hee Rhee, Nam Suk Sim, Chang Gon Kim, Hye Ryun Kim
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Tesfahun Dessale Admasu, John S. Yu
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Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy
Bryan Marr, Donghyeon Jo, Mihue Jang, Seung-Hwan Lee
Immune Network.2025;[Epub] CrossRef
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Chuan-Hsin Chang, Chih-Cheng Chien, Yue-Cune Chang
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Hye-Seong Park, Jun Eul Hwang, Je-Jung Lee, Woo Kyun Bae
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Integrin αvβ3 Induces HSP90 Inhibitor Resistance via FAK Activation in KRAS-Mutant Non-Small Cell Lung Cancer: Shinkyo Yoon, Hannah Yang, Hyun-Min Ryu, Eunjin Lee, Yujin Jo, Seyoung Seo, Deokhoon Kim, Chang Hoon Lee, Wanlim Kim, Kyung Hae Jung, Sook Ryun Park, Eun Kyung Choi, Sang-We Kim, Kang-Seo Park, Dae Ho Lee; Cancer Res Treat. 2022;54(3):767-781. Published online September 30, 2021; DOI: https://doi.org/10.4143/crt.2021.651

Abstract PDF Supplementary Material PubReader ePub

Purpose
Heat shock protein-90 (HSP90) remains an important cancer target because of its involvement in multiple oncogenic protein pathways and biologic processes. Although many HSP90 inhibitors have been tested in the treatment of KRAS-mutant non–small cell lung cancer (NSCLC), most, including AUY922, have failed due to toxic effects and resistance generation, even though a modest efficacy has been observed for these drugs in clinical trials. In our present study, we investigated the novel mechanism of resistance to AUY922 to explore possible avenues of overcoming and want to provide some insights that may assist with the future development of successful next-generation HSP90 inhibitors.
Materials and Methods
We established two AUY922-resistant KRAS-mutated NSCLC cells and conducted RNA sequencing to identify novel resistance biomarker.
Results
We identified novel two resistance biomarkers. We observed that both integrin Av (ITGAv) and β3 (ITGB3) induce AUY922-resistance via focal adhesion kinase (FAK) activation, as well as an epithelial-mesenchymal transition, in both in vitro and in vivo xenograft model. mRNAs of both ITGAv and ITGB3 were also found to be elevated in a patient who had shown acquired resistance in a clinical trial of AUY922. ITGAv was induced by miR-142 downregulation, and ITGB3 was increased by miR-150 downregulation during the development of AUY922-resistance. Therefore, miR-150 and miR-142 overexpression effectively inhibited ITGAvB3-dependent FAK activation, restoring sensitivity to AUY922.
Conclusion
The synergistic co-targeting of FAK and HSP90 attenuated the growth of ITGAvB3-induced AUY922-resistant KRAS-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome acquired AUY922-resistance in KRAS-mutant NSCLC.

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Triiodothyronine promotes the proliferation and chemoresistance of cholangiocarcinoma cells via HIF-1α/Glut1-stimulated glycolysis
Dihua Huang, Feng Xu, Luohang Xu, Zekai Tang, Yanxin Hu, Jiandong Li, Jianhua Yu
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Yoshinobu Kariya, Michiru Nishita
International Journal of Molecular Sciences.2025; 26(7): 3143. CrossRef
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Environmental Toxicology.2024; 39(12): 5238. CrossRef
Junctional adhesion molecular 3 (JAM3) is a novel tumor suppressor and improves the prognosis in breast cancer brain metastases via the TGF-β/Smad signal pathway
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Journal of Neuro-Oncology.2024; 170(2): 331. CrossRef
Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence
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Cancer and Metastasis Reviews.2023; 42(1): 217. CrossRef

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Management of Hypopharyngeal Carcinoma: Hong Gyun Wu, Hyung Joon Yoo, Charn Il Park, Kwang Hyun Kim, Young Kap Cho; J Korean Cancer Assoc. 1996;28(5):813-819.

Abstract PDF: Fifty-nine patients with squamous cell carcinoma of the hyphopharynx were treated at Seoul National University Hospital between October 1979 and December 1992. Of these, l8 patients received radiotherapy alone, 17 patients received planned surgery with neck dissection, followed by post-operative radiotherapy, and 24 patients received radiotherapy following 2 or 3 cycles of FP chemotherapy. A median follwo-up period was 41 months, ranged from 25 months to 129 months. The majority of the patients(94.9%, 56/59) was diagnosed with stage III(19%) or IV(75.9%). The overall survival at 5 years for all patients was 29%,with a median survival of 29 months. The 5-year survival rate was 15% on radiotherapy alone, 35% on surgery and postoperative radiotherapy, and 33% on 2 cyles of FP regimens followed by radiotherapy(p=0.001). However, the survival rates between surgery plus postoperative radiotherapy and chemotherapy following radiotherapy was not statistically significant, but voice preservation and swallowing function is superior with chemotherapy following radiotherapy. Although there was no randomized studies of surgery and postoperative radiotherapy versus chemothrapy following radiotherapy, nonsurgical management of advanced hypopharyngeal cancer employing chemothrapy and radiotherapy is preferred to radical surgery for patients with squamous cell carcinoma of the hypopharynx.

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