Overcoming Acquired Resistance through Combinatorial Therapy

The Tolani laboratory studies targeted therapies, both small molecules and biologics, to inhibit signal transduction pathways, including but not limited to the Hedgehog/Gli pathway, in lung cancer. The lab's research program is focused on overcoming drug resistance by use of combination therapy; employing lower doses of two drugs whose combined effect is greater than either drug alone (synergy) to produce maximal cancer cell death. Thus, we identify and study synergistic pairs of small molecule inhibitors as a therapeutic strategy. We are also interested in targeting Cancer Stem Cells (CSCs) as these perpetrator populations are typically refractory to conventional chemotherapy. Hedgehog expression in CSCs (~1%) are thought to drive initiation, maintenance and survival post chemotherapy of tumor cells (99%) via paracrine mechanisms. In an effort to target the signal source of carcinogenesis, we study the use of biologics to inhibit these pathways. By employing a non-small cell lung cancer (NSCLC) model, we hope to gain fundamental insights that can be translated into clinical advances for patients.