Cancer Research and Treatment

Original Article

Secondary Cancer Risk in Breast Cancer with and without Radiotherapy: The Observational Health Data Sciences and Informatics (OHDSI) Cohort Study: Seok Kim, Dachung Boo, Sooyoung Yoo, Borham Kim, Kyubo Kim, Kwangsoo Kim, Eunhye Song, Junmo Kim, Hyun Gee Ryoo, Jin Chul Paeng, In Young Choi, SooJeong Ko, Ie Ryung Yoo, Rae Woong Park, Ho-Young Lee; Received October 8, 2024 Accepted June 4, 2025 Published online June 5, 2025; DOI: https://doi.org/10.4143/crt.2024.968 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Radiotherapy is used to reduce the risk of breast cancer recurrence after surgery, but it is a potential cause of secondary cancer. We validated the risk of secondary cancer in primary breast cancer who received radiotherapy compared with those who did not from a matched cohort using a large-scale observational study of the Observational Health Data Sciences and Informatics (OHDSI) data network.
Materials and Methods
A retrospective comparative cohort study using propensity score-matched cohorts was performed using two Observational Medical Outcome Partnership common data model databases, from tertiary general hospitals in South Korea. Among female patients who underwent surgery after the diagnosis of breast cancer, the risk of secondary primary malignant occurrence after 1:1 matching was analyzed.
Results
Among 27,078 patients with breast cancer, there was no significant difference in the risk of secondary cancer following radiotherapy in 4,426 patients after 1:1 propensity-score matching. Further, there were no significant differences in the sensitivity analysis according to age, latency period, and number of radiation treatments.
Conclusion
There was no difference in the risk of secondary cancer in the patients diagnosed with breast cancer depending on whether or not radiotherapy was performed after surgery. In the future, it is necessary to analyze including data generated during cancer treatment.

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Review Article

Cellular Dormancy in Cancer: Mechanisms and Potential Targeting Strategies: Hye-Young Min, Ho-Young Lee; Cancer Res Treat. 2023;55(3):720-736. Published online March 22, 2023; DOI: https://doi.org/10.4143/crt.2023.468

Abstract PDF PubReader ePub

Cancer is a leading cause of disease-related mortality worldwide. Drug resistance is one of the primary reasons for the failure of anticancer therapy. There are a number of underlying mechanisms for anticancer drug resistance including genetic/epigenetic modifications, microenvironmental factors, and tumor heterogeneity. In the present scenario, researchers have focused on these novel mechanisms and strategies to tackle them. Recently, researchers have recognized the ability of cancer to become dormant because of anticancer drug resistance, tumor relapse, and progression. Currently, cancer dormancy is classified into “tumor mass dormancy” and “cellular dormancy.” Tumor mass dormancy represents the equilibrium between cell proliferation and cell death under the control of blood supply and immune responses. Cellular dormancy denotes the state in which cells undergo quiescence and is characterized by autophagy, stress-tolerance signaling, microenvironmental cues, and epigenetic modifications. Cancer dormancy has been regarded as the stem of primary or distal recurrent tumor formation and poor clinical outcomes in cancer patients. Despite the insufficiency of reliable models of cellular dormancy, the mechanisms underlying the regulation of cellular dormancy have been clarified in numerous studies. A better understanding of the biology of cancer dormancy is critical for the development of effective anticancer therapeutic strategies. In this review, we summarize the characteristics and regulatory mechanisms of cellular dormancy, introduce several potential strategies for targeting cellular dormancy, and discuss future perspectives.

Citations

Citations to this article as recorded by

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Bioactive Materials.2026; 56: 15. CrossRef
Dormant and activated polyploid giant cancer cells: From chemoradiotherapy resistance to cancer progression
Jiayue Liu, Kai Liu, Man Yan, Jing Xu, Yandi Liu, Shiwu Zhang
Cancer Letters.2026; 636: 218137. CrossRef
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Abdur Raheem Aleem, Atif Ali, Wajid Ali, Yuying Cheng, Zhibin Yan, Chaoyi Xia, Chenguang Liu, Caiyun Fu, Yiren Hu, Xi Wang
MedComm – Oncology.2026;[Epub] CrossRef
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Amos Olalekan Akinyemi, Md Rakibul Alam, Mithu Howlader, Mohammad Esfini Farahani, Lixiang Gu, Chun Li, Chripus Ngule, Kevin Fulp, Bolaji Owoyemi, Xinyi Wang, Samuel Nwadialo, Fatemeh Selani, Makumba Esoe, Obaleye Oluwafunminiyi, Zhiguo Li
iNew Medicine.2026;[Epub] CrossRef
Endoplasmic reticulum stress in skeletal muscle dysfunction of type 2 diabetes: mechanisms and therapeutic implications
Xin Wang, Mingdi Li, Zengpeng Chi, Mingshan Wang, Jiayi Liu, Ailin Li, Bailin Song, Le Tong
Frontiers in Endocrinology.2026;[Epub] CrossRef
Effect of postsurgical adjuvant chemotherapy timing on outcomes in patients with pancreatic cancer – a systematic review and meta-analysis
Longlan Zhou, Lin Zhang
Journal of Chemotherapy.2025; 37(6): 483. CrossRef
The changing treatment landscape of EGFR-mutant non-small-cell lung cancer
Fei Zhou, Haoyue Guo, Yang Xia, Xiuning Le, Daniel S. W. Tan, Suresh S. Ramalingam, Caicun Zhou
Nature Reviews Clinical Oncology.2025; 22(2): 95. CrossRef
Vaccine-induced T cell receptor T cell therapy targeting a glioblastoma stemness antigen
Yu-Chan Chih, Amelie C. Dietsch, Philipp Koopmann, Xiujian Ma, Dennis A. Agardy, Binghao Zhao, Alice De Roia, Alexandros Kourtesakis, Michael Kilian, Christopher Krämer, Abigail K. Suwala, Miriam Stenzinger, Halvard Boenig, Agnieszka Blum, Victor Murcia P
Nature Communications.2025;[Epub] CrossRef
Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence
Muhammad Tufail, Can-Hua Jiang, Ning Li
Military Medical Research.2025;[Epub] CrossRef
TFF3 facilitates dormancy of anti-estrogen treated ER+ mammary carcinoma
Shu Chen, Xi Zhang, Basappa Basappa, Tao Zhu, Vijay Pandey, Peter E. Lobie
Communications Medicine.2025;[Epub] CrossRef
ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review)
Lokman Varisli, Panagiotis Zoumpourlis, Demetrios Spandidos, Vassilis Zoumpourlis, Spiros Vlahopoulos
Oncology Letters.2025; 29(5): 1. CrossRef
Apoptotic cell-derived extracellular vesicles-MTA1 confer radioresistance in cervical cancer by inducing cellular dormancy
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Journal of Translational Medicine.2025;[Epub] CrossRef
Growth factor receptor plasticity drives therapeutic persistence of metastatic breast cancer
Mitchell Ayers, Marvis Monteiro, Aneesha Kulkarni, Julie W. Reeser, Emily Dykhuizen, Sameek Roychowdhury, Michael K. Wendt
Cell Death & Disease.2025;[Epub] CrossRef
A comprehensive transcriptome based meta-analysis to unveil the aggression nexus of oral squamous cell carcinoma
Soujanya J. Vastrad, Ganesan Rajalekshmi Saraswathy, Jagadish B. Dasari, Gouri Nair, Ashok Madarakhandi, Dominic Augustine, S.V. Sowmya
Biochemistry and Biophysics Reports.2025; 42: 102001. CrossRef
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Hazel Reeva, Godson Mahesh, Uma Manjunath, Nagarajan Selvamurugan, Durairaj MohanKumar
Seminars in Oncology.2025; 52(3): 152346. CrossRef
Enter sandman: how to tackle dormant breast cancer cells
Fouad Attieh, Reina Al Khatib, Marc Boutros, Antoine Mouawad, Hampig Raphaël Kourie
Medical Oncology.2025;[Epub] CrossRef
Diagnosis and therapeutic targeting of quiescent cancer cells: road to conquer cancer recurrence
Moon Jong Kim
BMB Reports.2025; 58(7): 277. CrossRef
Decoding the adaptive survival mechanisms of breast cancer dormancy
Francis M. Barnieh, Jamie Morton, Olaitan Olanrewaju, Sherif F. El-Khamisy
Oncogene.2025; 44(40): 3759. CrossRef
Comparative Analysis of Chemotherapy Resistance Mechanisms in Humans and Companion Animals
Daniel Luiz de Miranda Cravo, Pedro Antônio Bronhara Pimentel, Ana Paula Vargas Garcia, André Luiz de Moura Junqueira, Fabiana Sanches Soares, Antonio Giuliano, Angel Almendros, Rodrigo dos Santos Horta
Veterinary Sciences.2025; 12(8): 747. CrossRef
Autophagy in the regulation of cancer dormancy
Damla Gunes, Alara Ustal, Yusuf Emre Ertem, Yunus Akkoc, Devrim Gozuacik
FEBS Letters.2025; 599(16): 2272. CrossRef
Integrated single-cell RNA-seq analysis reveals that EZH2 regulates the MIF-CD74 axis to modulate T cell activation and exhaustion in hepatocellular carcinoma
Yangyang Zhou, Yi Xu, Mengfan Ye, Jiayi Xing, Di Chen, AL-Ameer Wail Hussein Ahmed, Al-Rahabi Rehab Abdullah Mohammed Ali, Chenwei Pan, Xiangchou Yang, Zan Shen
Journal of Translational Medicine.2025;[Epub] CrossRef
Targeted Therapies in the Most Common Advanced Solid Tumors, Drug Resistance, and Counteracting Progressive Micrometastatic Disease: The Next Frontier of Research
Andrea Nicolini, Paola Ferrari, Roberto Silvestri, Dario A. Bini
MedComm.2025;[Epub] CrossRef
An in vitro tumor recurrence model based on platinum-resistant colon cancer cells as a research tool for studying cancer cell dormancy
Alisa Morshneva, Olga Gnedina, Maria Igotti, Li Yang
PLOS One.2025; 20(10): e0333671. CrossRef
What Is Apoptosis and Why Is It Inhibited by the Most Important Tumor Suppressor (p53)?
Razmik Mirzayans
International Journal of Molecular Sciences.2025; 26(21): 10505. CrossRef
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Molecular Cancer.2025;[Epub] CrossRef
Unlocking Lung Cancer Cell Dormancy: An Epigenetic Perspective
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International Journal of Molecular Sciences.2025; 26(22): 10997. CrossRef
Sleepyhead, deadly awakening: the dynamics of metastatic organotropism, tumor dormancy and therapeutic implications
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Frontiers in Oncology.2025;[Epub] CrossRef
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Aziza Alshahrani, Arwa Alsubait, Zahrah Asiri, Sahar Alghamdi, Sarah Bin Saqyah, Tariq Alqahtani, Rawan Fitaihi, Njoud Altuwaijri, Yahya F. Jamous
Frontiers in Oncology.2025;[Epub] CrossRef
Microenvironmental and Molecular Pathways Driving Dormancy Escape in Bone Metastases
Mohamad Bakir, Alhomam Dabaliz, Ahmad Dawalibi, Khalid S. Mohammad
International Journal of Molecular Sciences.2025; 26(24): 11893. CrossRef
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Yaqing Zuo, Zhiwu Long, Rongrong Li, Yi Le, Silong Zhang, Huan He, Longjia Yan
European Journal of Medicinal Chemistry.2024; 265: 116106. CrossRef
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Evelyne Collignon
Current Opinion in Oncology.2024; 36(2): 74. CrossRef
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Yunqing Sun, Yang Chen, Zhenan Liu, Jingjing Wang, Junqiang Bai, Ruixue Du, Mingshu Long, Zhengjun Shang
Biomedicines.2024; 12(2): 305. CrossRef
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Biomedicine & Pharmacotherapy.2024; 176: 116783. CrossRef
Colorectal cancer and dormant metastases: Put to sleep or destroy?
Marina A Senchukova
World Journal of Gastrointestinal Oncology.2024; 16(6): 2304. CrossRef
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Haneef Ahmed Amissah, Stephanie E. Combs, Maxim Shevtsov
Cells.2024; 13(13): 1087. CrossRef
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Current Issues in Molecular Biology.2024; 46(8): 8340. CrossRef
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Putri Cahaya Situmorang, Syafruddin Ilyas, Sony Eka Nugraha, Rony Abdi Syahputra, Nik Mohd Afizan Nik Abd Rahman
Frontiers in Pharmacology.2024;[Epub] CrossRef
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Biological Research.2024;[Epub] CrossRef
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Chenfei Dong, Yang Liu, Suli Chong, Jiayue Zeng, Ziming Bian, Xiaoming Chen, Sairong Fan
International Journal of Molecular Sciences.2024; 25(17): 9502. CrossRef
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Journal of the Neurological Sciences.2024; 466: 123234. CrossRef
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Current Medicinal Chemistry.2024; 31(38): 6336. CrossRef
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Biochemistry (Moscow).2024; 89(12-13): 2155. CrossRef

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Special Article

How Can We Treat Cancer Disease Not Cancer Cells?: Kyu-Won Kim, Su-Jae Lee, Woo-Young Kim, Ji Hae Seo, Ho-Young Lee; Cancer Res Treat. 2017;49(1):1-9. Published online December 26, 2016; DOI: https://doi.org/10.4143/crt.2016.606

Abstract PDF PubReader ePub

Since molecular biology studies began, researches in biological science have centered on proteins and genes at molecular level of a single cell. Cancer research has also focused on various functions of proteins and genes that distinguish cancer cells from normal cells. Accordingly, most contemporary anticancer drugs have been developed to target abnormal characteristics of cancer cells. Despite the great advances in the development of anticancer drugs, vast majority of patients with advanced cancer have shown grim prognosis and high rate of relapse. To resolve this problem, we must reevaluate our focuses in current cancer research. Cancer should be considered as a systemic disease because cancer cells undergo a complex interaction with various surrounding cells in cancer tissue and spread to whole body through metastasis under the control of the systemic modulation. Human body relies on the cooperative interaction between various tissues and organs, and each organ performs its specialized function through tissue-specific cell networks. Therefore, investigation of the tumor-specific cell networks can provide novel strategy to overcome the limitation of current cancer research. This review presents the limitations of the current cancer research, emphasizing the necessity of studying tissue-specific cell network which could be a new perspective on treating cancer disease, not cancer cells.

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