1.DNA Damage and Nuclear Anaplasia Induced by Trastuzumab Deruxtecan in Cancer Cells with Variable HER2 Expression and Homologous Recombination Deficiency Status
So Hyeon KIM ; Yoonjung PARK ; Ahrum MIN ; Hye Yeon PARK ; Yu-Jin KIM ; Sujin HAM ; Jiwon KOH ; Seongyeong KIM ; Dae-Won LEE ; Han Suk RYU ; Jin-Soo KIM ; Kyung-Hun LEE ; Seock-Ah IM
Cancer Research and Treatment 2026;58(2):407-422
Purpose:
Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models.
Materials and Methods:
Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells.
Results:
T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed.
Conclusion
These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.
2.Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
Jiwon KOH ; Jinyong KIM ; Go-Un WOO ; Hanbaek YI ; So Yean KWON ; Jeongmin SEO ; Jeong Mo BAE ; Jung Ho KIM ; Jae Kyung WON ; Han Suk RYU ; Yoon Kyung JEON ; Dae-Won LEE ; Miso KIM ; Tae-Yong KIM ; Kyung-Hun LEE ; Tae-You KIM ; Jee-Soo LEE ; Moon-Woo SEONG ; Sheehyun KIM ; Sungyoung LEE ; Hongseok YUN ; Myung Geun SONG ; Jaeyong CHOI ; Jong-Il KIM ; Seock-Ah IM
Cancer Research and Treatment 2025;57(2):443-456
Purpose:
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods:
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results:
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.
3.Korean Practice Guidelines for Gastric Cancer 2024: An Evidence-based, Multidisciplinary Approach (Update of 2022 Guideline)
In-Ho KIM ; Seung Joo KANG ; Wonyoung CHOI ; An Na SEO ; Bang Wool EOM ; Beodeul KANG ; Bum Jun KIM ; Byung-Hoon MIN ; Chung Hyun TAE ; Chang In CHOI ; Choong-kun LEE ; Ho Jung AN ; Hwa Kyung BYUN ; Hyeon-Su IM ; Hyung-Don KIM ; Jang Ho CHO ; Kyoungjune PAK ; Jae-Joon KIM ; Jae Seok BAE ; Jeong Il YU ; Jeong Won LEE ; Jungyoon CHOI ; Jwa Hoon KIM ; Miyoung CHOI ; Mi Ran JUNG ; Nieun SEO ; Sang Soo EOM ; Soomin AHN ; Soo Jin KIM ; Sung Hak LEE ; Sung Hee LIM ; Tae-Han KIM ; Hye Sook HAN ; On behalf of The Development Working Group for the Korean Practice Guideline for Gastric Cancer 2024
Journal of Gastric Cancer 2025;25(1):5-114
Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.
4.Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
Jiwon KOH ; Jinyong KIM ; Go-Un WOO ; Hanbaek YI ; So Yean KWON ; Jeongmin SEO ; Jeong Mo BAE ; Jung Ho KIM ; Jae Kyung WON ; Han Suk RYU ; Yoon Kyung JEON ; Dae-Won LEE ; Miso KIM ; Tae-Yong KIM ; Kyung-Hun LEE ; Tae-You KIM ; Jee-Soo LEE ; Moon-Woo SEONG ; Sheehyun KIM ; Sungyoung LEE ; Hongseok YUN ; Myung Geun SONG ; Jaeyong CHOI ; Jong-Il KIM ; Seock-Ah IM
Cancer Research and Treatment 2025;57(2):443-456
Purpose:
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods:
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results:
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.
5.Korean Practice Guidelines for Gastric Cancer 2024: An Evidence-based, Multidisciplinary Approach (Update of 2022 Guideline)
In-Ho KIM ; Seung Joo KANG ; Wonyoung CHOI ; An Na SEO ; Bang Wool EOM ; Beodeul KANG ; Bum Jun KIM ; Byung-Hoon MIN ; Chung Hyun TAE ; Chang In CHOI ; Choong-kun LEE ; Ho Jung AN ; Hwa Kyung BYUN ; Hyeon-Su IM ; Hyung-Don KIM ; Jang Ho CHO ; Kyoungjune PAK ; Jae-Joon KIM ; Jae Seok BAE ; Jeong Il YU ; Jeong Won LEE ; Jungyoon CHOI ; Jwa Hoon KIM ; Miyoung CHOI ; Mi Ran JUNG ; Nieun SEO ; Sang Soo EOM ; Soomin AHN ; Soo Jin KIM ; Sung Hak LEE ; Sung Hee LIM ; Tae-Han KIM ; Hye Sook HAN ; On behalf of The Development Working Group for the Korean Practice Guideline for Gastric Cancer 2024
Journal of Gastric Cancer 2025;25(1):5-114
Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.
6.Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
Jiwon KOH ; Jinyong KIM ; Go-Un WOO ; Hanbaek YI ; So Yean KWON ; Jeongmin SEO ; Jeong Mo BAE ; Jung Ho KIM ; Jae Kyung WON ; Han Suk RYU ; Yoon Kyung JEON ; Dae-Won LEE ; Miso KIM ; Tae-Yong KIM ; Kyung-Hun LEE ; Tae-You KIM ; Jee-Soo LEE ; Moon-Woo SEONG ; Sheehyun KIM ; Sungyoung LEE ; Hongseok YUN ; Myung Geun SONG ; Jaeyong CHOI ; Jong-Il KIM ; Seock-Ah IM
Cancer Research and Treatment 2025;57(2):443-456
Purpose:
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods:
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results:
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.
7.Korean Practice Guidelines for Gastric Cancer 2024: An Evidence-based, Multidisciplinary Approach (Update of 2022 Guideline)
In-Ho KIM ; Seung Joo KANG ; Wonyoung CHOI ; An Na SEO ; Bang Wool EOM ; Beodeul KANG ; Bum Jun KIM ; Byung-Hoon MIN ; Chung Hyun TAE ; Chang In CHOI ; Choong-kun LEE ; Ho Jung AN ; Hwa Kyung BYUN ; Hyeon-Su IM ; Hyung-Don KIM ; Jang Ho CHO ; Kyoungjune PAK ; Jae-Joon KIM ; Jae Seok BAE ; Jeong Il YU ; Jeong Won LEE ; Jungyoon CHOI ; Jwa Hoon KIM ; Miyoung CHOI ; Mi Ran JUNG ; Nieun SEO ; Sang Soo EOM ; Soomin AHN ; Soo Jin KIM ; Sung Hak LEE ; Sung Hee LIM ; Tae-Han KIM ; Hye Sook HAN ; On behalf of The Development Working Group for the Korean Practice Guideline for Gastric Cancer 2024
Journal of Gastric Cancer 2025;25(1):5-114
Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.
8.Current practices in peripheral blood stem cell processing and cryopreservation:a nationwide survey of Korean transplant centers
Soo‑Kyung KIM ; Jaeeun YOO ; Jong‑Han LEE ; Ha‑Eun LEE ; Jae‑Sook AHN ; Kyung‑Nam KOH ; Byung‑Sik CHO ; Seong‑Kyu PARK ; Ho Joon IM ; Hyunji LEE ; Sun‑Young KONG
Blood Research 2025;60():41-
Purpose:
Processing methods for hematopoietic stem cells vary significantly across institutions, with no standardized guidelines currently in place. This lack of standardization presents challenges in ensuring consistent quality and out‑ comes of stem cell transplantation procedures. This study investigated current practices in peripheral blood stem cell (PBSC) processing and storage among transplant centers in Korea to establish a foundation for the development of standardized guidelines.
Methods:
A comprehensive questionnaire was distributed to 46 hematopoietic stem cell transplantation centers in Korea, examining five key areas: PBSC collection procedures, use of cryopreservatives, cryopreservation protocols, quality control measures, and thawing protocols.
Results:
Analysis of the 29 responses revealed significant variations across different stages of PBSC handling. All centers used controlled-rate freezers, and 92.9% stored cells at temperatures below -150 ◦ C . However, other prac‑ tices varied widely. Additional post-collection processing was performed by 53.8% of respondents. DMSO concen‑ trations ranged from 5 to 15%, with diverse combinations of supplementary media. Notably, 28.6% of patients did not undergo post-thaw quality assessment tests.
Conclusion
This study identified significant heterogeneity in PBSC processing practices across Korean transplant centers. These findings underscore the need for evidence-based standardized guidelines to ensure consistent product quality and improve transplantation outcomes.
9.The Awareness of Sports Physicians about Relative Energy Deficiency in Sport
Soo Hyun PARK ; Eon Sook LEE ; Jieun KWON ; Lina KIM ; Yeonsoo KIM ; Tae Kyung KIM ; Nayoung AHN ; Young Kill YUN ; Sun Joo LEE ; Young Sun LEE ; Hyo Jeong LEE ; Suk Ha JEON ; Tae Im YI
The Korean Journal of Sports Medicine 2024;42(4):247-2533
Purpose:
Relative energy deficiency in sport (REDs) is a syndrome of physiological and/or psychological functioning experienced by female and male athletes that is caused by exposure to problematic low energy availability. For the prevention and intervention of REDs, awareness of REDs among sports physicians is important, but it is largely unknown. This study aimed to survey the awareness and clinical treatment experience of REDs in sports physicians.
Methods:
We conducted an online survey to assess awareness of the triad and REDs among sports physicians and members of The Korean Society of Sports Medicine.
Results:
A total of 69 members (62.2% male, including sports physicians) to this survey. Most participants (84.1%) were aware of the triad compared to fewer with awareness regarding REDs (23.2%). People who knew about the difference between REDs and triad was 33.3%, which was lower than those who did not (66.6%). Only 10.1% of the study subjects had experience treating REDs patients, and the biggest difficulty in treating patients was a lack of information and education (50.7%). It appeared that the most information about REDs was obtained from academic conferences (59.4%).
Conclusion
This survey found relatively low awareness of REDs among physicians treating athletes and sports professionals. Considering the various negative effects of REDs on athlete health and performance, education and promotion are needed to increase awareness among sports physicians and sports professionals.
10.The Awareness of Sports Physicians about Relative Energy Deficiency in Sport
Soo Hyun PARK ; Eon Sook LEE ; Jieun KWON ; Lina KIM ; Yeonsoo KIM ; Tae Kyung KIM ; Nayoung AHN ; Young Kill YUN ; Sun Joo LEE ; Young Sun LEE ; Hyo Jeong LEE ; Suk Ha JEON ; Tae Im YI
The Korean Journal of Sports Medicine 2024;42(4):247-2533
Purpose:
Relative energy deficiency in sport (REDs) is a syndrome of physiological and/or psychological functioning experienced by female and male athletes that is caused by exposure to problematic low energy availability. For the prevention and intervention of REDs, awareness of REDs among sports physicians is important, but it is largely unknown. This study aimed to survey the awareness and clinical treatment experience of REDs in sports physicians.
Methods:
We conducted an online survey to assess awareness of the triad and REDs among sports physicians and members of The Korean Society of Sports Medicine.
Results:
A total of 69 members (62.2% male, including sports physicians) to this survey. Most participants (84.1%) were aware of the triad compared to fewer with awareness regarding REDs (23.2%). People who knew about the difference between REDs and triad was 33.3%, which was lower than those who did not (66.6%). Only 10.1% of the study subjects had experience treating REDs patients, and the biggest difficulty in treating patients was a lack of information and education (50.7%). It appeared that the most information about REDs was obtained from academic conferences (59.4%).
Conclusion
This survey found relatively low awareness of REDs among physicians treating athletes and sports professionals. Considering the various negative effects of REDs on athlete health and performance, education and promotion are needed to increase awareness among sports physicians and sports professionals.

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