Potential Role of Growth Factors in Diminishing Radiation Therapy Neural Tissue Injury

doi:10.1053/j.seminoncol.2005.03.012

Seminars in Oncology

Volume 32, Supplement 3, April 2005, Pages 67-70

https://doi.org/10.1053/j.seminoncol.2005.03.012 Get rights and content

Human growth factors are firmly established in treatment of cytopenias that are associated with cancer chemotherapy, and have been used successfully to reduce severe mucositis in patients receiving radiation therapy and chemotherapy in the setting of autologous bone marrow transplantation. The ability of growth factors that are involved in differentiation and proliferation of neural tissue cells to prevent or accelerate recovery from radiation injury currently is being evaluated in preclinical studies. Data from these studies indicate that brief therapeutic intervention with platelet-derived growth factor, insulin-like growth factor-1, vascular endothelial growth factor, and the combination of insulin-like growth factor-1 and basic fibroblast growth factor can prevent or delay radiation myelopathy after spinal cord irradiation. Additional investigation is required to define potentially clinically useful growth factor regimens in the clinic.

Section snippets

Effects of radiation on spinal cord tissue and role of growth factors in neural tissue repair

The impetus for exploring strategies for neural protection stemmed from the observation that the central nervous system has a large capacity to repair subclinical radiation injury. In a series of studies, Rhesus macaques were given increasing doses of single-course fractionated irradiation (2.2 Gy per fraction) yielding a clear dose-response effect in terms of spinal cord injury indicated by the increasing proportion of animals developing paresis as the dose increased from 70.4 to 83.6 Gy (Fig 1

Preclinical studies of radiation myelopathy

Our group has performed studies to test whether PDGF and IGF-1 can prevent radiation necrosis of the rat spinal cord and to establish potential dose-effect relationships.³ Adult Fisher F-344 rats received radiation to the cervical cord in two fractions over a 24-hour interval and concomitant administration of either intrathecal PDGF or saline as continous infusion for 4 days or three subcutaneous doses of IGF-1 or saline starting 24 hours before radiation therapy (RT). The doses of PDGF were

Conclusion

Growth-factor treatment is routinely used in the prevention of chemotherapy-related cytopenias. The concept of using growth factors to protect against radiation-induced mucositis has been established in mucositis models and validated in the autologous bone marrow transplantation setting. In the more complex setting of neural tissue injury, experimental studies in rodent models of radiation myelopathy have provided proof of principle that growth factors can have a protective effect for neural

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N.H. Andratschke et al.
Modulation of rodent spinal cord radiation tolerance by administration of platelet-derived growth factor
Int J Radiat Oncol Biol Phys
(2004)

There are more references available in the full text version of this article.

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: Supported by the Gilbert H. Fletcher Distinguished Chair supplemented by a grant of the Dr. Mildred Scheel Foundation for Cancer Research, Bonn, Germany.

¹: Dr Ang has served on an advisory board for Amgen.

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