Integration of Targeted New Agents with Chemotherapy
Development of new anti-cancer drugs that can more precisely target childhood cancers offers the prospect of more effective therapy with fewer side effects. More than 70% of children diagnosed with cancer today are cured of their disease, but today’s therapy has both short term and lifelong side effects, and too many children still die from their cancer. A critical challenge is how best to combine new anti-cancer drugs with potentially curative but toxic chemotherapy.
In this proposal, we present a way to study new drugs that will soon enter clinical trials in children with cancer, with a focus on how to best combine these drugs with conventional chemotherapy. We have selected 3 new targeted drugs that have shown promise in many laboratory tests and are already being evaluated in adults with cancer. We will study these novel drugs with the spectrum of chemotherapy drugs currently used by pediatric oncologists, by employing a variety of pediatric cancer cell lines that we can grow in the laboratory.
Our goal is to determine which chemotherapy drugs are best combined with each of these new targeted agents. The most promising combinations will then be studied in mouse models of the most common pediatric cancers.
Importantly, we will determine the drug concentrations that are necessary to observe beneficial effects. As in the past this is where too many promising drugs in the laboratory have failed to prove effective when tested in patients – the drug concentrations achieved in mice far exceeded the concentrations that could safely be achieved in man.
Our results will then be able to help guide the clinical trials of these anticancer drugs, and point the way forward for the next generation of combination clinical trials in children with cancer. With this research, we can be more confident of not sacrificing the important gains made with conventional chemotherapy in the treatment of childhood cancer, while paving the way for a transition to more targeted new cancer drugs with the potential of fewer short and long term side effects.