Attempts to optimize radiotherapy and chemotherapy efficacy with the use of targeted agents in rectal and prostate cancers : from animal models to early phase I/II clinical trials

Molecular-targeted agents are potent tumor inhibitors that target specific molecular pathways during carcinogenesis. They possess radio- and/or chemosensitizing properties which lead to many attempts to clinically combine these drugs with conventional radiotherapy and chemotherapy. Radiotherapy and chemotherapy play a central role in the management of prostate and rectal cancers. In locally advanced rectal cancer, chemoradiotherapy followed by curative surgery significantly reduces the risk of loco-regional relapse. Yet, disease-free survival and overall survival of patients are not improved. Previously, the addition of Epidermal Growth Factor Receptor-targeting drugs to chemoradiotherapy in rectal cancer resulted only in limited efficacy. The results showed an inferior rate of complete pathologic response compared to chemoradiation alone. It is therefore necessary to optimize the integration of EGFR-targeting drugs to preoperative chemoradiation in order to improve the long-term clinical outcome of patients with locally advanced rectal cancer. In prostate cancer, patient’s prognosis declines dramatically at the onset of metastasis. Metastatic prostate cancer initially responds to androgen deprivation therapy but would eventually progress to a state of castration-resistant disease for which therapeutic options become limited. Encouraging data from clinical trials using angiogenesis-targeting agents have motivated researchers to further evaluate whether the blockade of this biological pathway would add benefits to chemotherapy in metastatic castration-resistant prostate cancer.(MED - Sciences médicales) -- UCL, 201