Most of the current therapies against epithelial cancers, including chemotherapy and targeted agents, are aimed at the tumor epithelia alone. This approach, however, ignores the stromal micro-environment in which tumors grow.
The stroma is a complex environment of fibroblasts, blood and lymphatic vessels, nerves, inflammatory cells, and extracellular matrix that provide the structure, nutrients, and growth factors for tumor growth, maintenance, and metastasis. Combination therapy targeting both tumor epithelial and stromal compartments may yield greater results than current therapeutics that target only the tumor epithelium.
We have focused on non-small lung cancer to study the tumor epithelia and stromal interactions. Through the lens of the Hedgehog (Hh) signaling pathway, we probe the molecular response of stromal fibroblasts in response to Hh ligands secreted by lung cancer epithelia and how these stromal responses alter the tumor epithelia for proliferation and metastasis.
We use genetic, chemical, and biochemical strategies in cultured lung cancer cell lines with autochthonous genetic mouse models of lung cancer for our studies.