Complementary Drugs

Program researchers are developing new pharmacologic and biologic agents to use in combination with radiotherapy and chemotherapy. By amplifying treatment effectiveness, these agents help improve local tumor control, prevent metastatic spread and minimize toxicity to healthy tissues.

Because solid tumors-which make up more than 90% of all cancers-typically have areas of hypoxia, or very low oxygenation, researchers are particularly interested in understanding and exploiting hypoxic tumor physiology. Much of this effort is focused on:

Identifying secreted markers induced by tumor hypoxia. These markers can be used to determine the prognosis of patients with solid tumors. Several hypoxia markers have already been identified by program researchers that may help predict tumor relapse and survival in head and neck squamous cell carcinoma (HNSCC) patients.

Developing hypoxia-targeted agents that selectively amplify the effects of radiation and chemotherapy on tumor cells while sparing normal cells. This work has already led to a number of advances, including the first hypoxia-activated drug, benzotriazine di-N-oxide (TPZ), which shows promise in the care of HNSCC patients. New hypoxia-targeted strategies under development include exploiting the natural affinity of the bacteria Clostridium sporogenes for anaerobic environments and targeting new drugs to regions with elevated levels of the HIF-1 transcription factor, a common indicator of hypoxia.

Enhancing the combined use of radiation with chemotherapy and/or surgery. Today most solid tumors are treated with a multimodal approach combining radiotherapy, chemotherapy and/or surgery. To ensure these modalities effectively complement each other, program researchers are investigating their interactions and the optimal sequence for their delivery. One focus of study is exploring the effect of hypoxia on tumor sensitivity to radiation and chemotherapy.