Webster Cavenee, Ph.D.
Ludwig Institute for Cancer Research
University of California at San Diego
Developmental Regulation by FKHR Family Members Associated with Cancer
Background:
The onset, as well as the increase of malignancy of human cancers, is a result of the occurrence and accumulation of genetic defects. In many types of cancer, these genetic defects involve either the under-expression of tumor suppressor genes, over-expression of tumor causing genes (oncogenes), or both scenarios.
One mechanism for these genes to become dysregulated is called chromosome translocation, in which a part of the genetic material becomes dislocated from the original site and fuses itself with another gene. This type of abnormal fusion has been documented to trigger oncogene activation for leukemia and lymphoma. Although some solid tumors of children, such as rhabdomyosarcomas (tumors of muscle), can also arise as a result of chromosome translocation, much less is known about the genes involved in this process.
Project Director and Research:
As the director of the Ludwig Institute for Cancer Research, San Diego Branch, Dr. Cavenee and his team have been investigating the action of mutations in genes that lead to the heritability, development, and malignant progression of tumors.
With NFCR's support, Dr. Cavenee is currently working on identifying the regulatory mechanisms of a type of chromosome translocator, the FKHR gene family. Genes in this family code for molecules that play critical roles in the early stage of cell division. The abnormal fusion of FKHR with another gene (PAX3) is likely to have carcinogenic effects on the developing precursor cells. Moreover, Dr. Cavenee's data demonstrated that in addition to being a regulator of multiple "worker" genes, FKHR is also essential to the formation of the vascular system (angiogenesis) around tumor cells.
Dr. Cavenee's focus at this stage is to understand how FKHR influences angiogenesis, the targets and regulators of FKHR genes, as well as how other genes within this family affect the cellular transformation process. Hopefully, by mapping out how developing cells acquire genetic defects, we will be able to devise therapeutic measures that can prevent or inhibit these events from taking place.
Impact on Cancer Prevention, Treatment, or Cure:
Curing cancer has always been the ultimate goal for NFCR supported scientists, and we choose to accomplish this goal through basic science cancer research. In order to develop effective treatments, we must first figure out the initial genetic errors that lead a cell to become cancerous, and Dr. Cavenee's work is bringing us one more step closer to finding the answer to this seminal question. By understanding the fundamental issue of how genes influence cellular maturation and division, better strategies can be developed to prevent the onset of cancer.