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Is It Still Possible to Think about HSP70 as a Therapeutic Target in Onco-Hematological Diseases?
Nayla Mouawad1, Guido Capasso1, Edoardo Ruggeri1
1Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, 35128 Padua, Italy.
Abstract:
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 excursus, 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.
Insights
Heat Shock Protein of 70kDa (HSP70) is crucial for cancer cell survival and therapy resistance in hematologic malignancies. Despite its potential as a therapeutic target, HSP70 inhibitors have not yet reached clinical application.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hematologic malignancies remain incompletely understood, driving the search for novel therapeutic targets.
- Heat Shock Protein of 70kDa (HSP70), a key cytoprotective molecule, is implicated in apoptosis resistance and pathogenesis.
- HSP70 is upregulated in various onco-hematological diseases, correlating with poor prognosis and treatment resistance.
Purpose of the Study:
- To review the therapeutic potential of HSP70 as a target in hematologic malignancies.
- To explore HSP70-targeting strategies, including mono- and combination-therapies.
- To examine the role of HSP70 partners, such as HSF1 and co-chaperones, in therapeutic approaches.
Main Methods:
- Literature review of discoveries related to HSP70 in onco-hematology.
- Analysis of HSP70's role in apoptosis resistance and cell survival.
- Investigation of HSP70's correlation with prognosis and therapy resistance.
Main Results:
- HSP70 is a consistent finding across diverse hematologic cancers, linked to adverse outcomes.
- HSP70's cytoprotective functions make it an attractive target for overcoming treatment resistance.
- The druggability of HSP70 and its partners offers potential therapeutic avenues.
Conclusions:
- HSP70 represents a promising therapeutic target for acute/chronic leukemias, multiple myeloma, and lymphomas.
- Targeting HSP70, alone or in combination, could overcome resistance mechanisms in hematologic cancers.
- Despite extensive research, the clinical translation of HSP70 inhibitors remains a challenge.
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