Article
Oncology
Tim Grob, Mathijs A. Sanders, Christian M. Vonk, Francois G. Kavelaars, Melissa Rijken, Diana W. Hanekamp, Patrycja L. Gradowska, Jacqueline Cloos, Yngvar Floisand, Marinus van Marwijk Kooy, Markus G. Manz, Gert J. Ossenkoppele, Lidwine W. Tick, Violaine Havelange, Bob Lowenberg, Mojca Jongen-Lavrencic, Peter J. M. Valk
Summary: The study demonstrates that the next-generation sequencing-based detection of FLT3-ITD MRD predicts the risk of relapse and overall survival in patients with AML. The prognostic value of FLT3-ITD MRD exceeds that of other established clinical and molecular prognostic factors, highlighting its significance as a clinically relevant biomarker for dynamic disease risk assessment in AML.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Medicine, General & Internal
Harry P. Erba, Pau Montesinos, Hee-Je Kim, Elzbieta Patkowska, Radovan Vrhovac, Pavel Zak, Po -Nan Wang, Tsvetomir Mitov, James Hanyok, Yasser Mostafa Kamel, Jaime E. Connolly Rohrbach, Li Liu, Aziz Benzohra, Arnaud Lesegretain, Jorge Cortes, Alexander E. Perl, Mikkael A. Sekeres, Herve Dombret, Sergio Amadori, Jianxiang Wang, Mark J. Levis, Richard F. Schlenk
Summary: The aim of the study was to compare the effect of Quizartinib versus placebo on overall survival in patients with FLT3-ITD-positive newly diagnosed AML. The results showed that the addition of Quizartinib to standard chemotherapy can improve overall survival in adult patients with FLT3-ITD-positive newly diagnosed AML.
Article
Oncology
Mahran Shoukier, Tapan Kadia, Marina Konopleva, Ahmad S. Alotaibi, Mansour Alfayez, Sanam Loghavi, Keyur P. Patel, Rashmi Kanagal-Shamanna, Jorge Cortes, Bachar Samra, Elias Jabbour, Guillermo Garcia-Manero, Koichi Takahashi, Sherry Pierce, Nicholas J. Short, Musa Yilmaz, Koji Sasaki, Lucia Masarova, Naveen Pemmaraju, Gautam Borthakur, Hagop M. Kantarjian, Farhad Ravandi, Courtney D. DiNardo, Naval Daver
Summary: The combination of FLT3 inhibitor-based therapy with cytotoxic chemotherapy or low-intensity therapy appears to be effective in patients with FLT3-ITD/IDH co-mutated disease in both the frontline and recurrent and/or refractory settings. Fewer dual-mutated patients received cytotoxic chemotherapy or low-intensity therapy with an IDH1/2 inhibitor in the frontline setting; however, excellent responses also were observed with this approach.
Review
Hematology
Alexander J. Ambinder, Mark Levis
Summary: Aberrant FLT3 receptor signaling is common in AML and has significant clinical implications, with FLT3 inhibitors transforming the management of FLT3-mutated AML. However, questions remain regarding the optimal approach to treatment for these patients.
Article
Oncology
Corinna Spohr, Teresa Poggio, Geoffroy Andrieux, Katharina Schoenberger, Nina Cabezas-Wallscheid, Melanie Boerries, Sebastian Halbach, Anna L. Illert, Tilman Brummer
Summary: The presence of internal tandem duplications (ITD) in FMS-like tyrosine kinase 3 (FLT3) combined with DNMT3A mutations in acute myeloid leukemia (AML) leads to poor prognosis. Studies have shown that GAB2 is essential for the development of Flt3-ITD driven AML, with Gab2 deficient mice displaying prolonged survival and reduced pathology. Gab2 increases signaling of receptor tyrosine kinases, promoting AML aggressiveness and drug resistance, making it a promising biomarker and therapeutic target in human AML.
Article
Oncology
Pierre-Yves Dumas, Arnaud Villacreces, Amelie V. Guitart, Ali El-habhab, Layal Massara, Olivier Mansier, Audrey Bidet, Delphine Martineau, Solene Fernandez, Thibaut Leguay, Arnaud Pigneux, Isabelle Vigon, Jean-Max Pasquet, Vanessa Desplat
Summary: The study revealed that gilteritinib exhibited a stronger proapoptotic effect on FLT3-ITD AML cells in a simulated bone marrow microenvironment compared to quizartinib, and was more effective at targeting leukemia cells. Additionally, gilteritinib showed a toxicity profile on normal murine hematopoiesis similar to quizartinib.
CLINICAL CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Kun-Yin Qiu, Xiong-Yu Liao, Yong Liu, Ke Huang, Yang Li, Jian-Pei Fang, Dun-Hua Zhou
Summary: This study explores the relationship between FLT3/ITD allelic ratio and prognosis in pediatric AML patients and identifies an optimal threshold value, highlighting the importance of individualized treatment for pediatric AML.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Hiroto Inaba, Jolieke G. van Oosterwijk, John C. Panetta, Lie Li, Daelynn R. Buelow, James S. Blachly, Sheila Shurtleff, Ching-Hon Pui, Raul C. Ribeiro, Jeffrey E. Rubnitz, Stanley Pounds, Sharyn D. Baker
Summary: The combination therapy of crenolanib and sorafenib shows good efficacy and tolerability in FLT3-ITD positive AML, with rare emergence of FLT3-KD mutations.
CLINICAL CANCER RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Fangfang Wang, Jingcao Huang, Tingting Guo, Yuhuan Zheng, Li Zhang, Dan Zhang, Fujue Wang, Duolan Naren, Yushan Cui, Xiaoyan Liu, Ying Qu, Hongmei Luo, Yan Yang, Haichen Wei, Yong Guo
Summary: The combination treatment of HHT with quizartinib has shown synergistic effects on inhibiting cell growth, inducing apoptosis, and prolonging survival in mice with FLT3-ITD AML, suggesting it as a promising therapeutic strategy.
BIOCHEMICAL PHARMACOLOGY
(2021)
Editorial Material
Hematology
Sara E. Meyer
Summary: In this issue of Blood, Li et al.1 explore the role of FLT3 internal tandem duplication (ITD) in orchestrating transcriptional and epigenetic programs in myeloid progenitor cells, resulting in distinct functional outputs.
Article
Oncology
Naval Daver, Alexander E. Perl, Joseph Maly, Mark Levis, Ellen Ritchie, Mark Litzow, James McCloskey, Catherine C. Smith, Gary Schiller, Terrence Bradley, Ramon Tiu, Kiran Naqvi, Monique Dail, Deanna Brackman, Satya Siddani, Jing Wang, Brenda Chyla, Paul Lee, Jessica K. Altman
Summary: Combining gilteritinib with venetoclax has shown promising results in treating relapsed/refractory FLT3-mutated AML, with high rates of response and molecular remission regardless of prior FLT3 inhibitor therapy.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Erica Kao, Navin Pinto, Angela Trobaugh-Lotrario, Gail H. Deutsch, Yu Wu, Wenjing Wang, Erin R. Rudzinski, Yajuan J. Liu
Summary: In this study, two cases of extra-renal pediatric spindle cell neoplasms with EGFR internal tandem duplications are reported. This is the first reported example of EGFR ITDs in extra-renal tumors. Broad testing for this group of tumors is necessary to identify potential therapeutic targets.
GENES CHROMOSOMES & CANCER
(2022)
Article
Oncology
Jasmin Straube, Theresa Eifert, Therese Vu, Yashaswini Janardhanan, Rohit Haldar, Bjoern von Eyss, Leanne Cooper, Claudia Bruedigam, Victoria Y. Ling, Emily Cooper, Ann-Marie Patch, Lars Bullinger, Tina M. Schnoeder, Megan Bywater, Florian H. Heidel, Steven W. Lane
Summary: Murine models are useful for studying AML subtypes and compound mutations. The Cre recombinase expression in a transgenic murine model can lead to aggressive leukemia phenotype, polyclonal expansion of FLT3(ITD/ITD) progenitor cells, differentiation block and activation of Myc-dependent gene expression programs. Our report highlights the potential risks and unexpected effects of Cre expression in investigating oncogenic mutations in murine cancer models.
Article
Cell Biology
Sivasundaram Karnan, Ichiro Hanamura, Akinobu Ota, Souichi Takasugi, Ayano Nakamura, Miyuki Takahashi, Kaori Uchino, Satsuki Murakami, Md Wahiduzzaman, Lam Quang Vu, Md Lutfur Rahman, Muhammad Nazmul Hasan, Toshinori Hyodo, Hiroyuki Konishi, Shinobu Tsuzuki, Kazuhiro Yoshikawa, Susumu Suzuki, Ryuzo Ueda, Masayuki Ejiri, Yoshitaka Hosokawa, Akiyoshi Takami
Summary: STAT5 activation in genetically modified FLT3-ITD knock-in human myeloid leukemia K562 cells upregulates CD52 expression, while the anti-CD52 antibody alemtuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) and shows antitumor effects in FLT3(ITD/WT) cells.
CELL DEATH DISCOVERY
(2021)
Article
Hematology
Hartmut Doehner, Daniela Weber, Julia Krzykalla, Walter Fiedler, Gerald Wulf, Helmut Salih, Michael Luebbert, Michael W. M. Kuehn, Thomas Schroeder, Hans Salwender, Katharina Goetze, Joerg Westermann, Lars Fransecky, Karin Mayer, Bernd Hertenstein, Mark Ringhoffer, Hans-Joachim Tischler, Sigrid Machherndl-Spandl, Anika Schrade, Peter Paschka, Verena Gaidzik, Frauke Theis, Felicitas Thol, Michael Heuser, Richard F. Schlenk, Lars Bullinger, Maral Saadati, Axel Benner, Richard Larson, Richard Stone, Konstanze Doehner, Arnold Ganser
Summary: This study evaluated the efficacy of midostaurin in combination with intensive chemotherapy, followed by allogeneic hematopoietic-cell transplantation (HCT) and a 1-year midostaurin maintenance therapy, in adult patients with acute myeloid leukemia (AML) and fms-related tyrosine kinase 3 (FLT3) internal tandem duplication (ITD). The results showed that adding midostaurin to intensive therapy significantly improved the outcome in both younger and older AML patients with FLT3-ITD.
Article
Oncology
Hana Kim, Soomin Ahn, Hongsik Kim, Jung Yong Hong, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Kyoung-Mee Kim, Seung Tae Kim
Summary: This study investigated the status of homologous recombination deficiency (HRD) in various solid tumor patients and found that HRD alone is not sufficient to predict the efficacy of immune checkpoint inhibitors (ICIs) in solid tumor patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Oncology
Bum Jun Kim, Hee-Jung Jee, Sun Young Rha, Hye Sook Han, Min-Hee Ryu, Se Hoon Park, Jong Gwang Kim, Woo Kyun Bae, Keun-Wook Lee, Do-Youn Oh, Ji-Hye Byun, Dong Sook Kim, Young Ju Suh, Hyonggin An, Dae Young Zang
Summary: In patients with HER2-positive gastric or gastro-esophageal junction adenocarcinoma, second-line treatment with ramucirumab plus paclitaxel showed a significantly higher objective response rate compared to patients with HER2-negative disease. However, the increased response to treatment did not correlate with an improvement in overall survival (OS).
Meeting Abstract
Oncology
Masatoshi Eto, Jae-Lyun Lee, Se Hoon Park, Norihiko Tsuchiya, Po-Jung Su, T. W. Chan, Chirag Jyotiker Desai, Alessandra Di Pietro, Jing Wang, Robert J. Laliberte, Seasea Gao, Howard Gurney
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Yohann Loriot, Petros Grivas, Ronald De Wit, Arjun Vasant Balar, Arlene O. Siefker-Radtke, Jakub Zolnierek, Tibor Csoszi, Sang Joon Shin, Se Hoon Park, Vagif Atduev, Mahmut Gumus, Yu-Li Su, Saziye Burcak Karaca, Hernan Cutuli, Mehmet Nahit Sendur, Calvin Jia, Karen O'Hara, Sonia Franco, Nobuaki Matsubara
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Ryul Kim, Jeeyun Lee, Ghee Young Kwon, Jung Yong Hong, Byong Chang Jeong, Se Hoon Park
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Hongsik Kim, Ryul Kim, Joohyun Hong, Ghee Young Kwon, Chan Kyo Kim, Won Park, Wan Song, Hyun Hwan Sung, Byong Chang Jeong, Jung Yong Hong, Se Hoon Park
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Arlene O. Siefker-Radtke, Andrea Necchi, Se Hoon Park, Jesus Garcia-Donas, Robert A. Huddart, Earle F. Burgess, Mark T. Fleming, Arash Rezazadeh Kalebasty, Begona Mellado, Sergei Varlamov, Monika Joshi, Ignacio Duran, Scott T. Tagawa, Yousef Zakharia, Sydney Akapame, Ademi E. Santiago-Walker, Manish Monga, Anne O'Hagan, Yohann Loriot
Summary: This study evaluated the long-term efficacy and safety of Erdafitinib in patients with locally advanced or metastatic urothelial carcinoma. The results showed consistent activity and manageable safety profile in these patients.
Article
Urology & Nephrology
Hyun Hwan Sung, Hana Kim, Ryul Kim, Chan Kyo Kim, Ghee Young Kwon, Won Park, Wan Song, Byong Chang Jeong, Se Hoon Park
Summary: This study assessed the safety and efficacy of gemcitabine and cisplatin as neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy in muscle-invasive bladder cancer. The results showed that the approach was feasible and effective in the treatment of muscle-invasive bladder cancer.
INVESTIGATIVE AND CLINICAL UROLOGY
(2022)
Article
Oncology
Thomas Powles, Se Hoon Park, Eric Voog, Claudia Caserta, Begona P. Valderrama, Howard Gurney, Haralabos Kalofonos, Sinisa Radulovic, Wim Demey, Anders Ullen, Yohann Loriot, Srikala S. Sridhar, Norihiko Tsuchiya, Evgeny Kopyltsov, Cora N. Sternberg, Joaquim Bellmunt, Jeanny B. Aragon-Ching, Daniel P. Petrylak, Robert J. Laliberte, Bo Huang, Nuno Costa, John A. Blake-Haskins, Petros Grivas
Summary: This summary discusses the initial results of the JAVELIN Bladder 100 study, which investigated the use of avelumab as maintenance treatment for advanced urothelial cancer patients. The study found that patients treated with avelumab lived approximately 7 months longer on average compared to those who received standard supportive care alone.
Article
Oncology
ByulA Jee, Eunjeong Seo, Kyunghee Park, Yi Rang Kim, Sun-ju Byeon, Sang Min Lee, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Se Hoon Park, Woong-Yang Park, Minyong Kang
Summary: This study analyzed the genomic and transcriptomic features of metastatic ccRCC patients treated with ICIs, identified three molecular subtypes, and determined specific features associated with response and survival rates. Additionally, the research revealed a novel gene, GATM, associated with PBRM1 mutation and having tumor suppressive features in ccRCC.
Article
Oncology
Sujin Hyung, Boram Han, Jaeyun Jung, Seung Tae Kim, Jung Yong Hong, Se Hoon Park, Dae Young Zang, Joon Oh Park, Young Suk Park, Kyoung-Mee Kim, Won Ki Kang, Jeeyun Lee
Summary: Aberrations in the FGFR2 gene can lead to the development and poor prognosis of cancer. The study found that FGFR2 amplification and fusion occurred in approximately 1.5% and 1.1% of gastrointestinal tract/genitourinary tract cancers, respectively, with gastric cancer being the most common. Patients with FGFR2 alteration had shorter overall survival and progression-free survival. Therefore, screening for FGFR2 aberrations in solid cancer patients is of great importance.
JOURNAL OF ONCOLOGY
(2022)
Article
Oncology
Hyunji Jo, Joohyun Hong, Hongsik Kim, Hye Ryeon Kim, Ghee Young Kwon, Kyung A. Kang, Sung Yoon Park, Chan Kyo Kim, Byung Kwan Park, Jae Hoon Chung, Wan Song, Minyong Kang, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Se Hoon Park
Summary: Among patients with poor risk metastatic renal cell carcinoma (mRCC), first-line immune checkpoint inhibitor (ICI)-based therapy shows significantly longer overall survival (OS) and progression-free survival (PFS), as well as a higher response rate (RR), compared to tyrosine kinase inhibitor (TKI) monotherapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jun Su Park, Jeong Il Yu, Do Hoon Lim, Heerim Nam, Young Il Kim, Jeeyun Lee, Won Ki Kang, Se Hoon Park, Seung Tae Kim, Jung Yong Hong, Tae Sung Sohn, Jun Ho Lee, Ji Yeong An, Min Gew Choi, Jae Moon Bae
Summary: In this study, the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer was investigated. The results showed that absolute monocyte count (AMC) was the most relevant prognostic factor for overall survival and recurrence-free survival. Furthermore, adjuvant concurrent chemoradiotherapy (CCRT) improved recurrence-free survival in patients with a high absolute lymphocyte count (ALC).
Article
Biochemistry & Molecular Biology
Joohyun Hong, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park
Summary: The treatment of metastatic urothelial carcinoma after failure with platinum-based chemotherapy and immune checkpoint inhibitors remains controversial. This study found that participation in clinical trials and having a good performance status are associated with benefits from subsequent therapy for pretreated mUC.
Article
Oncology
Brian A. Van Tine, Anders Krarup-Hansen, Lisa M. Hess, Albiruni R. Abdul Razak, Victoria Soldatenkova, Jennifer Wright, Se Hoon Park
Summary: In the ANNOUNCE trial, patients with advanced or metastatic sarcoma receiving doxorubicin therapy reported clinical issues with physical function and pain, with a rapid decline in PROs observed during treatment. Patients with poorer symptoms at baseline tended to receive less doxorubicin therapy. Detailed summary data from the patient perspective during doxorubicin-based treatment can inform future care for these patients and aid in the development of PRO endpoints in future trials.