Is It Still Possible to Think about HSP70 as a Therapeutic Target in Onco-Hematological Diseases?

• Published in: Biomolecules (Basel, Switzerland) Vol. 13; no. 4; p. 604
• Main Authors: Mouawad, Nayla, Capasso, Guido, Ruggeri, Edoardo, Martinello, Leonardo, Severin, Filippo, Visentin, Andrea, Facco, Monica, Trentin, Livio, Frezzato, Federica
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.03.2023; MDPI
• Subjects: Apoptosis; Apoptosis - physiology; Blood diseases; Cancer therapies; Care and treatment; Cells; Cyclin-dependent kinases; Drug resistance; Health aspects; Heat Shock Proteins; Heat-Shock Proteins - metabolism; Hematological diseases; Hematology; HSF1 protein; HSP70; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; Humans; Kinases; Leukemia; Lymphoma; Malignancy; Medical prognosis; Molecular Chaperones; Multiple Myeloma; myeloma; Physiological aspects; Physiology; Review; RNA polymerase; Therapeutic applications; Therapeutic targets; therapeutics; Transcription Factors - metabolism; Italy; leukemia; therapeutics; HSP70; myeloma; Heat Shock Proteins; lymphoma
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom13040604

The search for molecules to be targeted that are involved in apoptosis resistance/increased survival and pathogenesis of onco-hematological malignancies is ongoing since these diseases are still not completely understood. Over the years, a good candidate has been identified in the Heat Shock Protein of 70kDa (HSP70), a molecule defined as "the most cytoprotective protein ever been described". HSP70 is induced in response to a wide variety of physiological and environmental insults, allowing cells to survive lethal conditions. This molecular chaperone has been detected and studied in almost all the onco-hematological diseases and is also correlated to poor prognosis and resistance to therapy. In this review, we give an overview of the discoveries that have led us to consider HSP70 as a therapeutic target for mono- or combination-therapies in acute and chronic leukemias, multiple myeloma and different types of lymphomas. In this , we will also consider HSP70 partners, such as its transcription factor HSF1 or its co-chaperones whose druggability could indirectly affect HSP70. Finally, we will try to answer the question asked in the title of this review considering that, despite the effort made by research in this field, HSP70 inhibitors never reached the clinic.