Molecularly Targeted Agents as Radiosensitizers in Cancer Therapy—Focus on Prostate Cancer

Abstract

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer.

Inhibition of Fatty Acid Synthase Sensitizes Prostate Cancer Cells to Radiotherapy

“…However, the potential of FASN inhibitors to radiosensitize tumors has not been evaluated. Radiotherapy is an important element in the clinical management of prostate cancer and its efficacy is expected to be enhanced when combined with radiosensitizing agents (48). We demonstrated that the radiation-induced decrease in the surviving fraction of PC3 clonogens was enhanced when C75 was administered in combination with X irradiation.…”

Incidental Dose to Pelvic Nodal Regions in Prostate-Only Radiotherapy

“…Moreover, concurrent androgen deprivation is known to have a radiosensitizing effect on the primary. 22,23 Extrapolating this to the nodes, and based on the above data, it is likely that incidental dose of about 36 to 40 Gy received by the obturator region in the present study may be adequate in eradicating microscopic disease.…”

Bioluminescence Tomography–Guided Radiation Therapy for Preclinical Research

“…In radiation therapy, studies in small animal models are a key means to understand and develop treatments for a wide spectrum of diseases (1, 2). Several groups, including ours, have initiated efforts to develop small animal irradiators that mimic human treatment (3–12).…”