PROteolysis TArgeting Chimeras (
PROTACs) degrade target
proteins via the
ubiquitin-
proteasome system, providing novel insights into
drug development for
hematologic malignancies.
PROTACs outperform conventional
therapeutics and currently available small molecule inhibitors in terms of efficacy, tissue-and cell-selectivity, and side effect profile. Most importantly,
PROTACs are a powerful tool for addressing "undruggable" oncogenic
proteins. Despite their numerous benefits,
PROTACs as
therapeutics face many challenges not only in the design and synthesis but also in the evaluation of anticancer effects and clinical application. In this article, we focus on
PROTACs that have demonstrated preclinical efficacy and clinical potential in the treatment of various
hematologic malignancies in the last 5 years. We start with a brief overview of the functioning mechanism and major breakthroughs in this field. To provide a balanced perspective on
PROTACs, we discuss the pros and cons of exploiting
PROTACs for therapeutic purposes. Following that, we brainstorm ideas to optimize
PROTACs for clinical application. More
PROTACs will enter clinical trials soon, benefiting patients with
hematologic malignancies.