Article
Multidisciplinary Sciences
Yi Rao, Zachary Samuels, Lukas M. Carter, Sebastien Monette, Sandeep Surendra Panikar, Patricia M. R. Pereira, Jason S. Lewis
Summary: HER2 is overexpressed in various cancers. Combining trastuzumab with lutetium-177 can deliver radiation to gastric tumors with minimal toxicity. Lovastatin can enhance cell surface HER2 levels and improve the therapeutic efficacy of [177Lu]Lu-DOTA-trastuzumab.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biotechnology & Applied Microbiology
Saori Mishima, Kohei Shitara
Summary: T-DXd has shown significantly higher objective response rate and longer overall survival in HER2-positive AGC patients with two or more previous lines of systemic chemotherapy, including trastuzumab. Its safety profile is acceptable. Currently, there are several ongoing clinical trials of T-DXd in combination with cytotoxic chemotherapy or an immune checkpoint inhibitor.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2021)
Review
Oncology
Jane E. Rogers, Kohei Yamashita, Matheus Sewastjanow-Silva, Allison Trail, Rebecca E. Waters, Jaffer Ajani
Summary: Human epidermal growth factor receptor-2 (HER2) is a well-known cancer target with various therapies available. However, the response and effectiveness of HER2-targeted agents differ among different tumor types, including gastric adenocarcinomas (GACs). GACs exhibit heterogeneity in HER2 expression, both within and between tumors, which poses challenges in assessing the efficacy of HER2-targeted agents. The recent approval of trastuzumab deruxtecan, an antibody drug conjugate, for refractory HER2-positive advanced GAC patients shows promise. Ongoing research aims to understand resistance patterns and intra-tumor heterogeneity to improve treatment outcomes. This review discusses the current status of HER2-targeted therapy in GACs and explores new therapies under investigation.
Article
Oncology
Shukui Qin, Jiafu Ji, Rui-Hua Xu, Wei Wang, Yong Tang, Feng Bi, Jin Li, Kang Wang, Jian-Ming Xu, Qingxia Fan, Wuyun Su, Lin Shen
Summary: The study aimed to evaluate the safety and effectiveness of trastuzumab plus chemotherapy in Chinese patients with HER2-positive metastatic gastric cancer. Results showed that trastuzumab treatment improved patients' overall survival and progression-free survival, with a safety profile consistent with previous knowledge.
Article
Oncology
Preeti Narayan, Asma Dilawari, Christy Osgood, Zhou Feng, Erik Bloomquist, William F. Pierce, Samina Jafri, Shyam Kalavar, Marina Kondratovich, Prakash Jha, Soma Ghosh, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Laleh Amiri-Kordestani
Summary: The US FDA approved fam-trastuzumab deruxtecan-nxki for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer. This is the first approved therapy specifically for HER2-low metastatic breast cancer.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Daisuke Kotani, Kohei Shitara
Summary: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate for HER2-positive gastric cancer, showing potential anti-tumor activities in preclinical and clinical studies. In a phase II trial, T-DXd demonstrated higher objective response rate and longer overall survival in patients with pretreated HER2-positive advanced gastric cancer.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yinxing Zhu, Xuedan Zhu, Xiaowei Wei, Cuiju Tang, Wenwen Zhang
Summary: Molecular targeted therapy focusing on the HER-2 signaling pathway in gastric cancer has gained attention, with trastuzumab being the only approved drug for HER-2 positive advanced gastric cancer. Ongoing research is developing novel HER2-targeted drugs, and clinical trials are exploring various approaches to overcome resistance and improve treatment outcomes for HER2-positive gastric cancer patients.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Review
Oncology
Jiyun Lee, Yeon Hee Park
Summary: Trastuzumab deruxtecan has demonstrated significant clinical benefits in HER2+ metastatic breast cancer patients, with an objective response rate of 60.9% and a unique side effect of pneumonitis. It has shown promising antitumor efficacy in HER2-low-expressing metastatic breast cancer. However, caution should be taken regarding the side effects, particularly lung inflammation.
Review
Oncology
Giandomenico Roviello, Giuseppe Aprile, Alberto D'Angelo, Luigi Francesco Iannone, Franco Roviello, Karol Polom, Enrico Mini, Martina Catalano
Summary: Gastric cancer is a common malignancy worldwide, with HER2 expression playing a key role in treatment. Resistance to therapy and novel treatment approaches are the current focus of research.
Article
Oncology
Mikiko Suzuki, Shigehiro Yagishita, Kiyoshi Sugihara, Yusuke Ogitani, Tadaaki Nishikawa, Mayu Ohuchi, Takashi Teishikata, Takahiro Jikoh, Yasushi Yatabe, Kan Yonemori, Kenji Tamura, Kosei Hasegawa, Akinobu Hamada
Summary: The study used PID imaging analysis to assess the intratumor pharmacokinetics of T-DXd, a novel HER2-targeted antibody-drug conjugate. The results demonstrated that T-DXd is distributed to tumor tissues via trastuzumab in a HER2-dependent manner and then spreads to adjacent HER2-negative areas. This successful visualization of the intratumoral distribution of T-DXd also illustrated its mechanism of action, known as the bystander effect.
CLINICAL CANCER RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Alice Indini, Erika Rijavec, Francesco Grossi
Summary: The review highlights the significant improvement of HER2-targeted therapies in breast and gastric cancer, as well as their potential application in NSCLC and colorectal cancer, focusing on the pharmacologic characteristics, efficacy, and toxicity profile of T-DXd. The article also discusses the latest clinical trial results of T-DXd in solid tumors and ongoing research on combination therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Nina E. Weisser, Mario Sanches, Eric Escobar-Cabrera, Jason O'Toole, Elizabeth Whalen, Peter W. Y. Chan, Grant Wickman, Libin Abraham, Kate Choi, Bryant Harbourne, Antonios Samiotakis, Andrea Hernandez Rojas, Gesa Volkers, Jodi Wong, Claire E. Atkinson, Jason Baardsnes, Liam J. Worrall, Duncan Browman, Emma E. Smith, Priya Baichoo, Chi Wing Cheng, Joy Guedia, Sohyeong Kang, Abhishek Mukhopadhyay, Lisa Newhook, Anders Ohrn, Prajwal Raghunatha, Matteo Zago-Schmitt, Joseph D. Schrag, Joel Smith, Patricia Zwierzchowski, Joshua M. Scurll, Vincent Fung, Sonia Black, Natalie C. J. Strynadka, Michael R. Gold, Leonard G. Presta, Gordon Ng, Surjit Dixit
Summary: In this study, the authors engineered an anti-HER2 biparatopic antibody, zanidatamab, with multiple mechanisms of action, including induction of HER2 clustering to trigger complement-dependent cytotoxicity, signal inhibition, antibody-dependent cellular cytotoxicity, and phagocytosis. Zanidatamab showed superior in vivo antitumor activity compared to tras + pert in a HER2-expressing xenograft model.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Jiangping Yang, Jiaqi Han, Yalan Zhang, Muhelisa Muhetaer, Nianyong Chen, Xi Yan
Summary: Through cost-effectiveness analysis, we found that T-DXd is more cost-effective than T-DM1 for patients with HER2-positive metastatic breast cancer in the US, but not in China at current drug prices.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Shihao Wang, Suliman Khan, Ghulam Nabi, Hong-Yu Li
Summary: Gastric cancer is a common cancer type with poor prognosis, especially in metastatic disease. The overexpression of HER2 is a major contributor to poor prognosis in HER2-positive advanced gastric cancer, and resistance to trastuzumab is a significant problem. Modulation of circadian clock genes may offer a solution to overcome trastuzumab resistance. This review discusses the association between circadian clock and cancer progression, development, and treatment, and proposes metformin-based chronotherapy as a potential approach to disrupt glycolysis oscillation and overcome trastuzumab resistance.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medicine, General & Internal
Toshihiko Matsumoto, Shogo Yamamura, Tatsuki Ikoma, Yusuke Kurioka, Keitaro Doi, Shogen Boku, Nobuhiro Shibata, Hiroki Nagai, Takanobu Shimada, Takao Tsuduki, Takehiko Tsumura, Masahiro Takatani, Hisateru Yasui, Hironaga Satake
Summary: This study analyzed the data of patients with HER2-positive advanced gastric cancer who received trastuzumab deruxtecan (T-DXd) and found that pre-administration of immune checkpoint inhibitors and a sufficiently long trastuzumab-free interval may be predictive factors of T-DXd efficacy.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Chie Kudo-Saito, Takahiro Miyamoto, Hiroshi Imazeki, Hirokazu Shoji, Kazunori Aoki, Narikazu Boku
Article
Oncology
Markus Moehler, Mikhail Dvorkin, Narikazu Boku, Mustafa Ozguroglu, Min-Hee Ryu, Alina S. Muntean, Sara Lonardi, Marina Nechaeva, Arinilda C. Bragagnoli, Hasan S. Coskun, Antonio Cubillo Gracian, Toshimi Takano, Rachel Wong, Howard Safran, Gina M. Vaccaro, Zev A. Wainberg, Matthew R. Silver, Huiling Xiong, Janet Hong, Julien Taieb, Yung-Jue Bang
Summary: The use of avelumab as maintenance therapy after first-line chemotherapy did not show superior overall survival compared to continued chemotherapy in patients with advanced GC or GEJC, regardless of PD-L1 status. Treatment-related adverse events occurred in both groups, with more severe events in the continued chemotherapy group.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Narikazu Boku, Taroh Satoh, Min-Hee Ryu, Yee Chao, Ken Kato, Hyun Cheol Chung, Jen-Shi Chen, Kei Muro, Won Ki Kang, Kun-Huei Yeh, Takaki Yoshikawa, Sang Cheul Oh, Li-Yuan Bai, Takao Tamura, Keun-Wook Lee, Yasuo Hamamoto, Jong Gwang Kim, Keisho Chin, Do-Youn Oh, Keiko Minashi, Jae Yong Cho, Masahiro Tsuda, Taihei Nishiyama, Li-Tzong Chen, Yoon-Koo Kang
Summary: The study confirmed the long-term efficacy of nivolumab in patients with advanced gastric cancer, showing a longer overall survival compared to placebo. Nivolumab also demonstrated potential benefits in the treatment beyond disease progression.
Article
Oncology
Eisuke Booka, Chiyo K. Imamura, Masashi Takeuchi, Hirofumi Kawakubo, Hiroya Takeuchi, Yusuke Tanigawara, Yuko Kitagawa, Narikazu Boku
Summary: This study evaluated the clinical validity of the S-1 dosage formula based on body surface area and creatinine clearance. The findings suggest that the refined formula can recommend an optimal dose in terms of safety and efficacy.
Article
Biochemistry & Molecular Biology
Masayuki Komatsu, Hitoshi Ichikawa, Fumiko Chiwaki, Hiromi Sakamoto, Rie Komatsuzaki, Makoto Asaumi, Kazuhisa Tsunoyama, Takeo Fukagawa, Hiromichi Matsushita, Narikazu Boku, Keisuke Matsusaki, Fumitaka Takeshita, Teruhiko Yoshida, Hiroki Sasaki
Summary: Frequent gene fusions of ARHGAP6/ARHGAP26 are found in peritoneally-metastasized gastric and pancreatic cancer, leading to downregulation of RhoA-ROCK-MLC2 signaling and cell death. The findings suggest the tumor-suppressive nature of ARHGAP-RhoA signaling and may provide a new avenue for drug discovery against this refractory cancer.
