Proteolysis-targeting chimeras (PROTACs) represent a promising class of drugs that can target disease-causing proteins more effectively than traditional small molecule inhibitors can, potentially revolutionizing drug discovery and treatment strategies. However, the links between in vitro and in vivo data are poorly understood, hindering a comprehensive understanding of the absorption, distribution, metabolism, and excretion (ADME) of PROTACs. In this work, ¹⁴C-labeled vepdegestrant (ARV-471), which is currently in phase III clinical trials for breast cancer, was synthesized as a model PROTAC to characterize its preclinical ADME properties and simulate its clinical pharmacokinetics (PK) by establishing a physiologically based pharmacokinetics (PBPK) model. For in vitro-in vivo extrapolation (IVIVE), hepatocyte clearance correlated more closely with in vivo rat PK data than liver microsomal clearance did. PBPK models, which were initially developed and validated in rats, accurately simulate ARV-471's PK across fed and fasted states, with parameters within 1.75-fold of the observed values. Human models, informed by in vitro ADME data, closely mirrored postoral dose plasma profiles at 30 mg. Furthermore, no human-specific metabolites were identified in vitro and the metabolic profile of rats could overlap that of humans. This work presents a roadmap for developing future PROTAC medications by elucidating the correlation between in vitro and in vivo characteristics.

In the past two decades,the United States made an impressed progress in the prevention and control of cancer that the overall morbidity and mortality of cancer had shown a downward trend, while China had seen an opposite trend. Cancer, one of the major public health concerns in China, has imposed an enormous burden onthe society and individuals. Therefore,in order to scientifically formulate cancer prevention and control policies, it is essential to make a comprehensive understanding of the practical experience in the field of cancer prevention and control from the United States. This article reviews the relevant literature on cancer trends as well as the prevention and control strategies in the United States,depictsthe cancer epidemic situation in the United States in the past 30 years, and summarizes the influencing factors, strategies and intervention experiences that lead to the improvement of cancer epidemic. It highlights the policy support, surveillance and intervention adopted by the United States for the cancer prevention and control. This article is expected to provide some implications and reference for the cancer prevention and control in China.

In the past two decades,the United States made an impressed progress in the prevention and control of cancer that the overall morbidity and mortality of cancer had shown a downward trend, while China had seen an opposite trend. Cancer, one of the major public health concerns in China, has imposed an enormous burden onthe society and individuals. Therefore,in order to scientifically formulate cancer prevention and control policies, it is essential to make a comprehensive understanding of the practical experience in the field of cancer prevention and control from the United States. This article reviews the relevant literature on cancer trends as well as the prevention and control strategies in the United States,depictsthe cancer epidemic situation in the United States in the past 30 years, and summarizes the influencing factors, strategies and intervention experiences that lead to the improvement of cancer epidemic. It highlights the policy support, surveillance and intervention adopted by the United States for the cancer prevention and control. This article is expected to provide some implications and reference for the cancer prevention and control in China.

In the past two decades,the United States made an impressed progress in the prevention and control of cancer that the overall morbidity and mortality of cancer had shown a downward trend, while China had seen an opposite trend. Cancer, one of the major public health concerns in China, has imposed an enormous burden onthe society and individuals. Therefore,in order to scientifically formulate cancer prevention and control policies, it is essential to make a comprehensive understanding of the practical experience in the field of cancer prevention and control from the United States. This article reviews the relevant literature on cancer trends as well as the prevention and control strategies in the United States,depictsthe cancer epidemic situation in the United States in the past 30 years, and summarizes the influencing factors, strategies and intervention experiences that lead to the improvement of cancer epidemic. It highlights the policy support, surveillance and intervention adopted by the United States for the cancer prevention and control. This article is expected to provide some implications and reference for the cancer prevention and control in China.