Article
Oncology
Ruoxi Hong, Wen Xia, Liye Wang, Kaping Lee, Qianyi Lu, Kuikui Jiang, Shengfeng Li, Jinquan Yu, Jin Wei, Weijia Tang, Danyang Zhou, Xin An, Jiajia Huang, Cong Xue, Xiwen Bi, Yanxia Shi, Zhongyu Yuan, Fei Xu, Shusen Wang
Summary: The study evaluated the safety, tolerability, pharmacokinetics, and anti-tumor activity of the novel drug BAT8001 targeting HER2-positive breast cancer patients. BAT8001 demonstrated promising anti-tumor activity and has the potential to provide a new therapeutic option for patients with metastatic HER2-positive breast cancer.
CANCER COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Ophelia Yin, Yuan Xiong, Seiko Endo, Kazutaka Yoshihara, Tushar Garimella, Malaz AbuTarif, Russ Wada, Frank LaCreta
Summary: This study characterized the pharmacokinetics of Trastuzumab deruxtecan in patients with HER2-positive breast cancer or other solid tumor malignancies. Results showed no significant differences in steady-state exposure of the drug in different patient populations, suggesting that dose adjustment based on specific patient characteristics is not necessary.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
Funda Meric-Bernstam, Emiliano Calvo, Keun Seok Lee, Victor Moreno, Yeon Hee Park, Sun Young Rha, Pavani Chalasani, Wei Zhong, Li Zhou, Steven Pirie-Shepherd, Abraham C. F. Leung, Giuseppe Curigliano
Summary: This study evaluated the safety and antitumor activity of PF-06804103 in patients with advanced/unresectable or metastatic breast and gastric cancers. The results showed that PF-06804103 demonstrated antitumor activity, but adverse events led to a high rate of treatment discontinuation.
MOLECULAR CANCER THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Blair Mcnamara, Michelle Greenman, Nicole Pebley, Levent Mutlu, Alessandro D. Santin
Summary: This review provides an overview of the application of antibody-drug conjugates (ADCs) as a targeted anti-cancer therapy, focusing on the use of HER2-targeting ADC therapy in gynecologic malignancies.
Article
Pharmacology & Pharmacy
Ophelia Yin, Hiroji Iwata, Chia-Chi Lin, Kenji Tamura, Junichiro Watanabe, Russ Wada, Helen Kastrissios, Malaz AbuTarif, Tushar Garimella, Caleb Lee, Lin Zhang, Javad Shahidi, Frank LaCreta
Summary: Trastuzumab deruxtecan (T-DXd) has been approved for HER2-positive metastatic breast cancer and gastric cancer, with the 5.4 mg/kg every-3-weeks dosage justified based on exposure-efficacy analysis. Intact T-DXd area under the concentration-time curve was significantly associated with objective response rate, while no significant exposure-response relationships were observed for duration of response or progression-free survival. Higher exposure to T-DXd or released drug was correlated with increased adverse events, suggesting a dose-response relationship with higher ORR and toxicity at 6.4 mg/kg compared to 5.4 mg/kg.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
Yinjuan Li, Lu Qi, Yu Wang, Xia Zhao, Shuzhen Lv, Yu Feng, Chen Liu, Pu Li, Bingjun Xiong, Yihui Guo, Dapeng Lv, Yongbo Liu, Ting Mao, Keyu Yuan, Xiaoqiang Cheng, Yanping Li, Xinghe Wang
Summary: SHR-A1201, an ADC combining trastuzumab with DM1, was investigated for its safety, tolerability, and pharmacokinetics in patients with advanced HER2-positive breast cancer. The phase I study enrolled 12 patients and administered SHR-A1201 at various doses, with most treatment-emergent adverse events being mild to moderate in severity. The maximum tolerated dose of SHR-A1201 was found to be no lower than that of T-DM1, and the drug exhibited typical ADC pharmacokinetics. The study showed promising antitumor effects and confirmed the tolerability and safety of SHR-A1201.
Article
Chemistry, Multidisciplinary
Seol Hwa Shin, Yun-Hee Park, Seok Soon Park, Eun Jin Ju, Jin Park, Eun Jeong Ko, Dong Jun Bae, Sang-Yeob Kim, Chul-Woong Chung, Ho Young Song, Se Jin Jang, Seong-Yun Jeong, Si Yeol Song, Eun Kyung Choi
Summary: LCB-ADC exhibits higher cytotoxicity compared to T-DM1 and effectively inhibits tumor growth in animal models with HER2 high expression. Furthermore, LCB-ADC demonstrates good efficacy in suppressing tumor growth in HER2-positive gastric cancer PDX model and T-DM1-resistant models.
Article
Immunology
James J. Harding, Ignacio Garrido-Laguna, Xiaoying Chen, Cynthia Basu, Afshin Dowlati, Alison Forgie, Andrea T. Hooper, Cris Kamperschroer, Steven I. Max, Allison Moreau, Megan Shannon, Gilbert Y. Wong, David S. Hong
Summary: P-cadherin is overexpressed in solid tumors, and PF-06671008 shows antitumor activity by engaging P-cadherin and CD3 epsilon. This phase 1 study evaluates the safety and tolerability of PF-06671008 and provides insights into managing immune-related adverse events. Limited antitumor activity and cytokine release syndrome were observed.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Lixi Li, Di Zhang, Binliang Liu, Dan Lv, Jingtong Zhai, Xiuwen Guan, Zongbi Yi, Fei Ma
Summary: Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the anti-tumor activity of cytotoxic drugs, and have shown potential as a promising treatment option for breast cancer and other tumors.
CHINESE MEDICAL JOURNAL
(2022)
Article
Engineering, Biomedical
Kwang Suk Lim, Daniel Y. Lee, Seungmin Han, David A. Bull, Young-Wook Won
Summary: HSP90 is crucial for cancer cell survival, and incorporating HSP90 inhibitors into antibodies through biological affinity binding can enhance targeted delivery and improve anti-cancer efficacy.
Review
Oncology
Veronique Debien, Evandro de Azambuja, Martine Piccart-Gebhart
Summary: Triple-positive breast tumors overexpress HER2 and are positive for HR expression. ER expression affects the response to anti-HER2 and associated systemic therapies. Optimizing dual anti-HER2 blockade is important for disease control in triple-positive tumors.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
Mark D. Pegram, Erika P. Hamilton, Antoinette R. Tan, Anna Maria Storniolo, Kemal Balic, Anton Rosenbaum, Meina Liang, Peng He, Shannon Marshall, Anita Scheuber, Mayukh Das, Manish R. Patel
Summary: MEDI4276 is a biparatopic tetravalent antibody targeting two nonoverlapping epitopes in subdomains 2 and 4 of the HER2 ecto-domain, demonstrating enhanced cellular internalization and cytolysis of HER2-positive tumor cells. In a first-in-human clinical trial, MEDI4276 showed clinical activity but intolerable toxicity at doses >0.3 mg/kg.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Genetics & Heredity
Mariana K. Najjar, Sara G. Manore, Angelina T. Regua, Hui-Wen Lo
Summary: HER2 overexpression is associated with poor prognosis in breast cancer, with HER2-targeted therapies, such as antibody-drug conjugates (ADCs), showing promising results in treating HER2-positive breast cancer. The development of ADCs leveraging the high specificity of HER2-targeted monoclonal antibodies with cytotoxic small molecules represents a significant advancement in the management of the disease.
Article
Oncology
Yongpeng Li, Lin Li, Haoyu Fu, Qing Yao, Lei Wang, Liguang Lou
Summary: The therapeutic management of HER2-positive malignancies involves the use of HER2-targeted antibody-drug conjugates (ADCs). Combining inhibitors of DNA damage repair and HER2-targeted ADCs may be a practical strategy for treating HER2-positive cancers.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Oncology
Yongpeng Li, Lin Li, Haoyu Fu, Qing Yao, Lei Wang, Liguang Lou
Summary: The therapeutic management of HER2-positive malignancies involves using HER2-targeted antibody-drug conjugates (ADCs), which release cytotoxic chemicals causing DNA damage and cell death. Combining DNA damage repair inhibitors with HER2-targeted ADCs shows synergistic anticancer effects in HER2-positive cancer cells. DS-8201, in combination with PARPi (AZD2281) and ATRi (BAY1895344), inhibits HER2-positive cancer cell growth, induces DNA damage and apoptosis, and has significant antitumor activity.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
