Boston University
College of Arts & Sciences
Office of the Dean
725 Commonwealth Avenue
Boston, MA 02215
T 617-353-2401
F 617-353-5374
For Immediate Release
Monday, March 5, 2012
CONTACT:
Patrick Farrell
Boston University
+1-617-358-1185
pmfarrel@bu.edu
BU researchers pursue promising new approach in
the treatment of liver cancer
Lead-based compound may be key to treating the fifth most common cancer
Hepatocellular carcinoma (HCC), or primary cancer of the liver, is the fifth most common
cancer worldwide. Despite the prevalence of this disease, until now there has been no
effective, systemic treatment. Thanks to a team of researchers in Boston University’s
departments of Biology and Chemistry, and the program in Molecular Biology, Cell Biology
& Biochemistry, that may be about to change.
The BU research team and collaborators recently discovered a promising new protein
target for chemotherapy in the treatment of liver cancer—the transcription factor LSF.
(Transcription factors are regulatory proteins that bind genomic DNA near the start of
genes, either promoting or inhibiting the transcription or copying of the gene.) LSF is found
in high levels in the tumor tissue of patients with liver cancer and has been demonstrated
to promote the development of cancer (oncogenesis) in studies using laboratory rodents.
Central to their findings, the BU scientists identified small molecules that effectively inhibit
LSF cellular activity, which in turn slows the growth of the cancer. In particular, one such
molecule, called Factor Quinolinone Inhibitor 1 (FQI1), derived from a lead compound, was
found to inhibit the ability of LSF to bind DNA both in extracts (in vitro, as determined by
electrophoretic mobility shift assays), and in cells. Consistent with inhibiting LSF activity,
FQI1 also eliminates the ability of LSF to turn up transcription. FQI1 also demonstrates
antiproliferative activity, or the ability to prevent or retard the growth of cells. While FQI1
quickly causes cell death in LSF-overexpressing cells, including liver cancer cells, healthy
cells are unaffected by the treatment. This phenomenon has been called oncogene
addiction, where tumor cells are “addicted” to the activity of an oncogenic factor for their
survival, but normal cells can do without it. This is very encouraging for use of such
compounds clinically.
Quantitative analysis of FQI1 (based on a concordant structure-activity relationship of a
panel of 23 quinolinones) strongly suggests that its growth inhibitory activity focuses on a
single biological target or family. This focus, coupled with the striking correlation between
the concentrations required for antiproliferative activity and for inhibition of LSF
transactivation indicates that LSF is that specific biological target of FQI1.
BU researchers pursue breakthrough
in the treatment of liver cancer
Page 2 of 3
Building on the in vitro trials, the researchers tested the efficacy of FQI1 in inhibiting liver
cancer tumor growth by injecting HCC cell lines into rodent models. FQI1 was observed to
significantly inhibit tumor growth with no observable side effects (general tissue
cytotoxicity). These dramatic findings support the further development of LSF inhibitors as
a promising new chemotherapy treatment for liver cancer.
The team’s findings have been published in the article “Antiproliferative small molecule
inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular
carcinoma” in the Proceedings of the National Academy of Science (PNAS) (citation details).
The co-principal investigators are Ulla Hansen, Professor of Biology, and Scott Schaus,
Associate Professor of Chemistry, Boston University.
Contributing authors are Trevor J. Grant, Girish Barot, Hang Gyeong Chin, Sarah Woodson,
Jennifer Sherman, and Tracy Meehan, Department of Biology, Boston University; Joshua A.
Bishop, Lisa M. Christadore, and John Kavouris, Department of Chemistry, Center for
Chemical Methodology and Library Development at Boston University; Sriharsa Pradhan,
New England BioLabs, Inc., Ipswich, MA; Ayesha Siddiq, Rachel Gredler, Xue-Ning Shen, and
Devanand Sarkar, Department of Human and Molecular Genetics, Virginia Commonwealth
University School of Medicine, Richmond, VA; Laura A. Briggs and William H. Andrews,
Sierra Sciences, LLC, Reno, NV; and Kevin Fitzgerald, Alnylam Pharmaceuticals, Inc.,
Cambridge, MA.
About Boston University—Founded in 1839, Boston University is an internationally
recognized private research university with more than 30,000 students participating in
undergraduate, graduate, and professional programs. As Boston University’s largest
academic division, the College and Graduate School of Arts & Sciences is the heart of the
BU experience with a global reach that enhances the University’s reputation for teaching
and research.
# # #
Contact information for the authors:
Ulla M. Hansen, Professor
Department of Biology
Boston University
5 Cummington St.
Boston, MA 02215
Office Phone: 617-353-8730
Email: uhansen@bu.edu
Website: www.bu.edu/biology/people/faculty/hansen/
BU researchers pursue breakthrough
in the treatment of liver cancer
Page 3 of 3
Contact information (cont’d)
Scott E. Schaus, Associate Professor
Department of Chemistry
Boston University
590 Commonwealth Ave.
Boston, MA 02215
Office Phone: 617-353-2489
Email: seschaus@bu.edu