Role of PROTACs in Hematological Malignancies

Hematological malignancies (HM) are among the most difficult types of cancer as far as management and treatment are concerned. There have been advancements in the treatment of HM, but despite the availability of targeted therapy or small molecules, clinical outcomes are not up to the mark. Relapse or refractory types of HM are even more difficult to treat. At the same time, the pathogenic role of various proteins has also been identified, and the available therapeutic approaches are only able to inhibit its function. Proteolysis targeting chimeras (PROTACs) are a group of hetero-bifunctional small molecules that cause pathogenic protein degradation instead of their inhibition by using a ubiquitin-proteasome system (UPS). PROTACs are considered superior to small molecules in terms of unique mechanisms of action, selectivity, and efficiency. Considering these facts, PROTACs emerged as a novel approach for targeted drug development for hematological malignancies. Currently, a few PROTACs are in the initial phase of a clinical trial, and many are under preclinical development. Therefore, in this section, we have precisely discussed the various protein targets or proteins of interest that have pathogenic in hematological malignancies and enlightened various PROTACs in terms of their efficacy, safety, developmental status, limitations, and future prospects.