Biao Luo, PhD
Assistant Research Professor
Office Phone: 215-728-5677
Institute for Personalized Medicine
Decades of experience and research in cancer care tells us that no two cancers are alike: some respond well to a particular therapy, while others, seemingly identical, do no respond at all. One reason for this discrepancy is that tumors, especially solid tumors, accumulate particular sets of mutations in many genes, and that these genes sets differ among individual patients. However, we now have the ability to determine genetic information in such tumors, and to act on this information when considering therapies. In this way, we hope to make the "one-size-fits-all" approach to cancer therapy a thing of the past.
In an effort to improve treatment of patients with cancer, Fox Chase Cancer Center has initiated a new program in which we aim to determine the genetic lesions that characterize tumors in living patients: the Institute for Personalized Medicine. The immediate objective of the Institute is to sequence exons from genes known to impact key, targetable, signaling pathways in patients with metastatic disease. Our vision is one in which at the time of diagnosis and again at disease progression, a patient's cancer will be sequenced either for selected genes of interest or the entire genome. The resultant information will be housed in a searchable database, thereby allowing patients to be matched to particular drugs based upon mechanism of action, regardless of the phase of clinical trial. Updated eligibility criteria will no longer state the requirement for a given disease but instead will articulate a far more sophisticated paradigm focusing on pathway activation, gene amplification, gene mutation, or combinations thereof.Top
Functional Characterization of Oncogenic Networks with High-Throughput shRNA Libraries
RNA interference (RNAi) is an important scientific discovery and a transforming technology that has greatly advanced somatic genetic studies of many organisms. In the last few years, I had been working on the development and application of high-throughput small hairpin RNA (shRNA) production and screening technologies. To characterize the functional basis of cancer, I have recently performed essential gene screens in 12 different cancer cell lines, in addition to modifier screens with several perturbagens. By integrating the functional signatures from essential gene screens with comprehensive genetic analyses of human tumors, we identified known and putative oncogenes, including BCR-ABL in CML, as well as EGFR, CDK4, and CRKL in non-small cell lung cancer. We further interrogated the BCR-ABL oncogenic network using modifier screens with Gleevec and shBCRABL. The broad application of this highly parallel genetic screening strategy will facilitate the rapid identification of genes that drive the malignant state. After the establishment of the functional importance of the putative cancer vulnerability genes, the signaling networks regulated by them can be further investigated by modifier screens against these genes, using genomewide shRNA libraries.Top