Background: Targeted drugs modulate selective pathways activated
or repressed only in cancer cells, resulting in a higher response to chemotherapy
with less severe side effects. The use of a selected member of the heat shock
protein 70 family (HSP70) as an effective therapeutic target in the treatment of
colorectal cancer (CRC) will be the focus of this review.
Methods: We generated two main questions for this study: 1) What are the current
and potential future molecular therapies in CRC? 2) Can selective members
of the HSP70 family advance drug design and drug discovery for treatment of
CRC patients? We discuss related articles based on their significance and translational
contributions to the existing literature.
Results: The first part of this review discusses molecularly targeted agents that are currently used
successfully in the clinic for the treatment of patients with CRC and highlights several novel targeted
agents that are being investigated in ongoing trials. The second part of this review focuses
on the unique tumorigenic functions of heat shock proteins, particularly mortalin-2, an essential
heat shock protein for mitochondrial biogenesis in normal cells and a dominant oncoprotein in
colon cancer cells. Basic and clinical studies have justified mortalin-2 as a potential molecular
target, and its inhibition could dramatically improve patients’ responses to standard chemotherapies.
Conclusion: Further understanding of the contributions of HSP70 family members to CRC at the
molecular level, combined with translation of new concepts into effective targeted therapies, are
anticipated to improve clinical outcomes and increase the therapeutic synergy with combination
treatment with cytotoxic agents.