Article
Biochemistry & Molecular Biology
Ernest Duah, Nathan D. Seligson, Avinash K. Persaud, Quynh Dam, Navjot Pabla, James W. Rocco, Junan Li, Ming Poi
Summary: Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths in the US, with HPV-negative cases having worse prognosis. Current treatment options mainly include chemotherapy, radiation, and surgery. This study investigated the therapeutic effects of CDK4/6 inhibitors in preclinical models of HNSCC, specifically abemaciclib, which showed inhibition of cell growth and induction of apoptosis. The combination of CDK4/6 and autophagy inhibitors synergistically decreased cell viability, induced apoptosis, and inhibited tumor growth, suggesting a potential therapeutic strategy for HNSCC.
MOLECULAR CARCINOGENESIS
(2023)
Article
Oncology
Monika Lukoseviciute, Stefan Holzhauser, Eleni Pappa, Tamoghna Mandal, Tina Dalianis, Ourania N. Kostopoulou
Summary: Neuroblastoma (NB), the most common solid extracranial tumor in children, often resists aggressive therapies and requires novel treatments. In this study, the combination of PI3K inhibitors with CDK4/6 or PARP inhibitors with WEE1 exhibited synergistic effects in NB cell lines, reducing viability and proliferation. Lower doses of these inhibitors could potentially reduce adverse effects.
Article
Biology
Zijie Cai, Jingru Wang, Yudong Li, Qianfeng Shi, Liang Jin, Shunying Li, Mengdi Zhu, Qi Wang, Lok Lam Wong, Wang Yang, Hongna Lai, Chang Gong, Yandan Yao, Yujie Liu, Jun Zhang, Herui Yao, Qiang Liu
Summary: CDK4/6 inhibitors are standard treatment for advanced HR+/HER2- breast cancer, but resistance is inevitable. This study found that overexpression of Cyclin D1 and CDK4 proteins leads to resistance, and targeting the PI3K/mTOR pathway can restore sensitivity.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Review
Oncology
Jinmeng Zhang, Dayu Xu, Yue Zhou, Zhengfei Zhu, Xi Yang
Summary: CDK4/6 inhibitors have shown potential as a new therapeutic agent for non-small cell lung cancer by preventing tumor cells from entering the G1 and S phases. Clinical studies have demonstrated some positive results, indicating the potential for future treatment options.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Qingfang Li, Yan Tie, Aqu Alu, Xuelei Ma, Huashan Shi
Summary: Head and neck cancer is a malignant and genetically complex disease that is difficult to treat. It is the sixth most common cancer, with tobacco, alcohol, and human papillomavirus as major risk factors. HNC is heterogeneous and treatment remains challenging. Despite current therapies, recurrence and metastasis are common, and resistance to chemotherapy and targeted therapies is a problem. Therefore, it is urgent to explore more effective and tolerable targeted therapies to improve outcomes for HNC patients.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Chemistry, Medicinal
Huifang Shan, Xinyu Ma, Guoyi Yan, Meng Luo, Xinxin Zhong, Suke Lan, Jie Yang, Yuanyuan Liu, Chunlan Pu, Yu Tong, Rui Li
Summary: A series of covalent CDK4/6 inhibitors were designed and synthesized, with compound C-13 showing potent anticancer activity in vitro and significant tumor growth inhibition in a mouse model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Medicine, General & Internal
Zhaomeng Guo, Kang Li, Peng Liu, Xiangmin Zhang, Jie Lv, Xianhai Zeng, Peng Zhang
Summary: Head and neck squamous cell carcinoma (HNSCC) originates from different parts of the head and neck, and the causes and molecular basis can vary. The tumor microenvironment (TME) consisting of various cells and molecules is crucial for the survival and spread of cancer cells. Understanding the interaction between tumor cells and the TME is essential for developing effective anti-cancer therapies.
FRONTIERS IN MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Naoya Kitamura, Shinya Sento, Yasumasa Yoshizawa, Eri Sasabe, Yasusei Kudo, Tetsuya Yamamoto
Summary: In recent years, drug therapy for head and neck squamous cell carcinoma (HNSCC) has made rapid progress, with a focus on molecular targeted therapy and immune checkpoint inhibitors in addition to traditional cytotoxic anti-cancer agents. While the importance of anti-cancer drug therapy continues to increase, current trends and future prospects of molecular targeted therapy in HNSCC are being explored in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Yuan Ke, Cheng-Gong Liao, Zheng-Qing Zhao, Xiao-Min Li, Rong-Jie Lin, Long Yang, He-Long Zhang, Ling-Min Kong
Summary: Combining ribociclib and pemetrexed showed a powerful ability to inhibit cancer proliferation, invasion, and metastasis, and it holds potential as a novel effective combinative therapy for patients with LUAD.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Sanjib Chaudhary, Ramesh Pothuraju, Satyanarayana Rachagani, Jawed A. Siddiqui, Pranita Atri, Kavita Mallya, Mohd W. Nasser, Zafar Sayed, Elizabeth R. Lyden, Lynette Smith, Siddhartha D. Gupta, Ranju Ralhan, Imayavaramban Lakshmanan, Dwight T. Jones, Apar Kishor Ganti, Muzafar A. Macha, Surinder K. Batra
Summary: This study demonstrates that the combination therapy of CDK4/6 and panEGFR inhibitors can significantly reduce tumor growth, induce cellular senescence, and regulate metabolic pathways in HNSCC, suggesting that dual targeting may be a critical therapeutic strategy in blocking tumor progression.
Article
Oncology
Peter Kar Han Lau, Carleen Cullinane, Susan Jackson, Rachael Walker, Lorey K. Smith, Alison Slater, Laura Kirby, Riyaben P. Patel, Bianca von Scheidt, Clare Y. Slaney, Grant A. McArthur, Karen E. Sheppard
Summary: The combination of adoptive cell transfer (ACT) with BRAF-MEK and CDK4/6 inhibitors has shown to be highly efficacious against BRAF(V600) melanoma, providing prolonged and deep anti-tumor responses. This study offers additional pre-clinical evidence to support the combination of BRAF-MEK-CDK4/6 inhibitors and ACT in clinical trials.
Article
Chemistry, Multidisciplinary
Tianyi Wang, Yaming Zhang, Kang Chen, Yi Huang, Yuwei Liu, Shuting Xu, Weiping Wang
Summary: Cell cycle progression is highly activated in cancer cells, and CDK4/6 inhibition-based cell cycle arrest is a potent cancer treatment strategy. Combining CDK4/6 PROTAC with Chlorin e6-based photodynamic therapy has a synergistic anti-cancer effect, mediated by mitochondria accumulation and activation, resulting in increased production of reactive oxygen species and apoptosis.
Article
Oncology
Agnieszka K. Witkiewicz, Emily Schultz, Jianxin Wang, Deanna Hamilton, Ellis Levine, Tracey O'Connor, Erik S. Knudsen
Summary: This study explored the features of HR+/HER2- breast cancer and its response to CDK4/6 inhibitors in a cohort of 280 patients. The results showed that modified SBR score and lack of PR expression were associated with poorer response to AI combinations. Gene expression analysis revealed significant changes in cell cycle and estrogen receptor signaling during treatment. Different gene expression subtypes were associated with treatment response and progression.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Masahiro Ohara, Kengo Saito, Ken Kageyama, Mizue Terai, Hanyin Cheng, Andrew E. Aplin, Takami Sato
Summary: Uveal melanoma (UM) is a common eye cancer in adults, with up to 50% of patients developing metastases. A preclinical study showed that combining CDK4/6 inhibitor with cMET inhibitor could provide significant clinical benefit to patients with metastatic uveal melanoma by suppressing tumor growth.
Article
Urology & Nephrology
Rebecca A. Sager, Sarah J. Backe, Elham Ahanin, Garrett Smith, Imad Nsouli, Mark R. Woodford, Gennady Bratslaysky, Dimitra Bourboulia, Mehdi Mollapour
Summary: The treatment of advanced and metastatic kidney cancer has improved with the introduction of new therapeutic options, including CDK4/6 inhibitors. Further research is needed to determine the best therapeutic approach for individual patients and how to overcome therapeutic resistance.
NATURE REVIEWS UROLOGY
(2022)
Correction
Genetics & Heredity
Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J. Yoon, Yang Yang, Inigo Martincorena, Chad J. Creighton, John N. Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J. Campbell, Han Liang
Correction
Genetics & Heredity
Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J. Yoon, Yang Yang, Inigo Martincorena, Chad J. Creighton, John N. Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J. Campbell, Han Liang
Summary: A revised version of this paper has been published and can be accessed through a link at the top.
Article
Oncology
Taofeek K. Owonikoko, Keunchil Park, Ramaswamy Govindan, Neal Ready, Martin Reck, Solange Peters, Shaker R. Dakhil, Alejandro Navarro, Jeronimo Rodriguez-Cid, Michael Schenker, Jong-Seok Lee, Vanesa Gutierrez, Ivor Percent, Daniel Morgensztern, Carlos H. Barrios, Laurent Greillier, Sofia Baka, Miten Patel, Wen Hong Lin, Giovanni Selvaggi, Christine Baudelet, Jonathan Baden, Dimple Pandya, Parul Doshi, Hye Ryun Kim
Summary: Maintenance therapy with nivolumab plus ipilimumab did not prolong overall survival (OS) for patients with extensive-disease small-cell lung cancer (ED-SCLC) who did not progress on first-line chemotherapy. However, there may be a benefit of nivolumab plus ipilimumab in patients with a tumor mutational burden of >= 13 mutations per megabase. The rates of grade 3-4 treatment-related adverse events were highest in the nivolumab plus ipilimumab group.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Michael Boyer, Mehmet A. N. Sendur, Delvys Rodriguez-Abreu, Keunchil Park, Dae Ho Lee, Irfan Cicin, Perran Fulden Yumuk, Francisco J. Orlandi, Ticiana A. Leal, Olivier Molinier, Nopadol Soparattanapaisarn, Adrian Langleben, Raffaele Califano, Balazs Medgyasszay, Te-Chun Hsia, Gregory A. Otterson, Lu Xu, Bilal Piperdi, Ayman Samkari, Martin Reck
Summary: The study showed that adding ipilimumab to pembrolizumab did not improve efficacy and was associated with greater toxicity in metastatic NSCLC patients.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Keunchil Park, Gee-Chen Chang, Giuseppe Curigliano, Wan-Teck Lim, Ross A. Soo, Miguel A. Molina-Vila, Valerie Cattan, Helene Darville, Eric Gandossi, Veronika Smutna, Isabelle Sudey, Santiago Viteri
Summary: The combination of gefitinib with S49076 showed limited anti-tumour activity with good tolerability in EGFR TKI-resistant NSCLC patients. The study did not reveal a clear trend in activity within specific molecular subsets due to the small number of eligible patients.
Article
Oncology
Hongsik Kim, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
Summary: Plasma EGFR mutation tests are commonly used for NSCLC patients developing resistance to EGFR inhibitors. This study found that the detection rate of T790M in subsequent tests was influenced by the presence of sensitizing mutations in initial plasma tests. The low sensitivity of the plasma test for T790M suggests the need for follow-up tissue or plasma tests.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Oncology
Keunchil Park, Eric B. Haura, Natasha B. Leighl, Paul Mitchell, Catherine A. Shu, Nicolas Girard, Santiago Viteri, Ji-Youn Han, Sang-We Kim, Chee Khoon Lee, Joshua K. Sabari, Alexander Spira, Tsung-Ying Yang, Dong-Wan Kim, Ki Hyeong Lee, Rachel E. Sanborn, Jose Trigo, Koichi Goto, Jong-Seok Lee, James Chih-Hsin Yang, Ramaswamy Govindan, Joshua M. Bauml, Pilar Garrido, Matthew G. Krebs, Karen L. Reckamp, John Xie, Joshua C. Curtin, Nahor Haddish-Berhane, Amy Roshak, Dawn Millington, Patricia Lorenzini, Meena Thayu, Roland E. Knoblauch, Byoung Chul Cho
Summary: Amivantamab demonstrates robust and durable responses with tolerable safety in patients with EGFR Exon20ins mutations, even after progression on platinum-based chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
D. Ross Camidge, Teresa Moran, Ingel Demedts, Heidrun Grosch, Kathryn Mileham, Julian Molina, Oscar Juan-Vidal, Gerold Bepler, Jonathan W. Goldman, Keunchil Park, Johan Wallin, Sameera R. Wijayawardana, Xuejing Aimee Wang, Volker Wacheck, Egbert Smit
Summary: This Phase II study examined the use of emibetuzumab to overcome acquired resistance to erlotinib in NSCLC patients with high MET protein expression levels. The study found that emibetuzumab did not effectively reverse resistance to erlotinib, although some patients experienced clinical benefit.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Remi Veillon, Hiroshi Sakai, Xiuning Le, Enriqueta Felip, Alexis B. Cortot, Egbert F. Smit, Keunchil Park, Frank Griesinger, Christian Britschgi, Yi-Long Wu, Barbara Melosky, Shobhit Baijal, Gilberto de Castro Jr, Michaela Sedova, Karin Berghoff, Gordon Otto, Paul K. Paik
Summary: The study demonstrated the safety and tolerability of tepotinib in patients with MET exon 14 skipping non-small cell lung cancer. Adverse events were mostly mild/moderate and manageable, with few withdrawals.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Yuichiro Doki, Makoto Ueno, Chih-Hung Hsu, Do-Youn Oh, Keunchil Park, Noboru Yamamoto, Tatsuya Ioka, Hiroki Hara, Manabu Hayama, Masahiro Nii, Keiko Komuro, Mariko Sugimoto, Makoto Tahara
Summary: This study evaluated the safety, tolerability, and antitumor activity of durvalumab monotherapy and durvalumab plus tremelimumab combination therapy in Asian patients with biliary tract cancer, esophageal squamous cell carcinoma, or head and neck squamous cell carcinoma. The results demonstrated acceptable safety profiles and clinical benefit in these patients.
Article
Oncology
Alexander Drilon, Vivek Subbiah, Oliver Gautschi, Pascale Tomasini, Filippo de Braud, Benjamin J. Solomon, Daniel Shao-Weng Tan, Guzman Alonso, Juergen Wolf, Keunchil Park, Koichi Goto, Victoria Soldatenkova, Sylwia Szymczak, Scott S. Barker, Tarun Puri, Aimee Bence Lin, Herbert Loong, Benjamin Besse
Summary: In this study, selpercatinib demonstrated durable and robust responses in both previously treated and treatment-naive patients with RET fusion-positive NSCLC, including intracranial activity.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Hyun Ae Jung, Jinyeong Lim, Yoon-La Choi, Jhingook Kim, Keunchil Park
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Byoung Chul Cho, Herbert H. F. Loong, Chun-Ming Tsai, Man Lung P. Teo, Hye Ryun Kim, Sun Min Lim, Suyog Jain, Steve Olsen, Keunchil Park
Summary: Plasma-based next-generation sequencing provides timely and clinically informative mutational genomic profiling for advanced non-squamous NSCLC in East Asian patients.
Meeting Abstract
Oncology
Dong-Wan Kim, Sang-We Kim, D. Ross Camidge, Naiyer A. Rizvi, Kristen A. Marrone, Xiuning Le, Collin Blakely, Keunchil Park, Gee-Chen Chang, Sandip Pravin Patel, Zachary A. Cooper, Rakesh Kumar, Ramin Samadani, Rebecca McCombs, Michael Pluta, Kevin Yufeng Wu, Suresh Ramalingam
Correction
Oncology
Makoto Nishio, Takashi Seto, Martin Reck, Edward B. Garon, Chao-Hua Chiu, Kiyotaka Yoh, Fumio Imamura, Keunchil Park, Jin-Yuan Shih, Carla Visseren-Grul, Bente Frimodt-Moller, Annamaria Zimmermann, Gosuke Homma, Sotaro Enatsu, Kazuhiko Nakagawa