個人簡歷

Education/Training:

Ph.D. in the Institute of Food Science and Technology, National Taiwan University

Selected Publications:

To date, Dr. Kuo has published more than 100 SCI articles, amassing a total of 5,153 citations, with an H-index of 48 and an i10-index of 88. Remarkably, her instrumental role in the development of four cancer treatment drug candidates (DBPR104, DBPR112, DBPR114, and DBPR216) has been pivotal to their achievement of Investigational New Drug (IND) approvals from both the US FDA and Taiwan FDA for clinical studies. DBPR104 (a vascular disrupting agent) has completed a Phase II clinical trial in Taiwan, while Phase I or I/II clinical trials for DBPR112 (an ErbB kinase inhibitor), DBPR114 (a multikinase inhibitor), and DBPR216 (a multikinase inhibitor) are ongoing. Among her publications, several stand out for their significant impact in the field. Selected publications include: Theranostics (PMID: 33859744); J Med Chem (PMID: 34337952; 28609101; 26653033); Eur J Med Chem (PMID: 34929581; 26519930); J Food Drug Anal (PMID: 35649133); J Biomed Sci (PMID: 29592811); Free Radic Biol Med (PMID: 29080842; 22245092; 22001324); Int J Cancer (PMID: 25693518; 17597106); Chem Res Toxicol (PMID: 26275128); Biochem Pharmacol (PMID: 23933386); J Agric Food Chem (PMID: 21561091); Cancer Res (PMID: 15231674).

Abstract

Chinese Title:

毒理學視角下：分子標靶、藥物特性及替代測試在癌症新藥研發的影響與意義

English Title:

From a toxicology perspective: The impact and significance of molecular targets, drug properties, and alternative testing in the discovery and development of new cancer drugs

Abstract

The success rate of drug development is around 5%, as each drug must undergo a lengthy, high-risk journey from discovery through preclinical studies and three phases of clinical trials to achieve market approval. Despite extensive efforts, most drug candidates are abandoned due to safety, efficacy, or other challenges, resulting in only a small percentage ultimately reaching the market. Key factors contributing to drug development failures include the suitability of molecular targets, safety or toxicity challenges in the candidates, and the relevance of research models to clinical conditions. Drawing from my research, I will discuss NRF2 as a target paradigm. Given critical role of NRF2 in fundamental physiological processes, overly activating or inhibiting NRF2 can lead to adverse effects, making the precise regulation of its activity a crucial yet challenging aspect of drug design. I will also discuss my research on IDO1 inhibitor development, where lead compounds have faced unforeseen toxicity challenges. IDO1 is an enzyme crucial for immune regulation via tryptophan metabolism, a pathway exploited by tumors to evade immune responses. I will highlight how toxicity issues in a promising compound impacted its development. The FDA Modernization Act 2.0 has accelerated the adoption of alternative testing models, encouraging less reliance on animal testing. My research integrates patient-derived xenograft (PDX) platforms with alternative models to enhance clinical relevance in preclinical testing while adhering to the 3Rs principle of animal reduction. These advancements not only align with ethical standards but also pave the way for more precise targeting, improved safety profiles, and more clinically relevant cancer treatment models—ultimately advancing the development of safer and more effective therapies.