Kinder, Gentler Chemotherapy: Centrosome Cluster Busters
Utilizing chemical genetic approaches and state-of-the-art technology, we are identifying cancer-specific drug targets for chemoprevention and chemotherapy. Our research strategies draw from a broad base including synthetic medicinal chemistry, molecular and cellular biology to gain insights about drug targets and mechanisms, and animal models to study the kinetics of tumor growth and inhibition and drug pharmacokinetic profiles.
Our team has extensively studied a family of anticancer agents called noscapinoids, which are derivatives of the plant-derived alkaloid noscapine. Noscapine subtly modulates microtubule dynamicity, so it is non-toxic. Our lab has rationally designed and characterized the biological activities of several noscapinoids with enhanced anticancer efficacy that maintain safety profiles similar to that of the parent compound.
We have also studied anticancer agents called centrosome declustering drugs, of which several noscapinoids are members. In contrast with normal tissues, cancer cells often harbor excess centrosomes, which impart aggressive phenotypes like chromosomal instability and augmented migratory capacity and invasiveness. Centrosome declustering drugs disperse these centrosomes and cause cell death during mitosis. Normal cells do not have supernumerary centrosomes and are unaffected by these drugs, making this a highly selective chemotherapeutic strategy.