2010 UALC
Kwok-Kin Wong, MD, PhD
Dana-Farber Cancer Institute
Research Project:
The impact of CHD7 genomic rearrangement in small cell lung cancer pathogenesis
Summary:
Our understanding of the genetic causes of SCLC is very limited. Recently, analysis of the entire genome of SCLC tumors revealed a number of recurrent genetic alterations in the CHD7 gene, found in several human SCLC lines. This proposal will further investigate this genetic alteration to understand how this change can cause SCLC, validating a new target for future therapeutics.
More Content:
Final Report
Dr. Wong has completed his studies, but has found that changing the expression of CHD7 in vitro and in vivo did not yield any change in the phenotype of small cell lung cancer. This raises the strong possibility that CHD7 genetic alteration might not be an oncogenic driver and instead might be a passenger mutation. However, during the course of these studies, Dr. Wong’s lab has generated a large colony of RB/p53 mutant mice harboring small cell lung cancer. Using these mice, the team will perform treatment studies with cisplatin/ectoposide, the standard treatment given to SCLC patients, treating the models until acquired resistance develops. This will be an unique platform to study mechanisms of acquired resistance in human SCLC patients. Dr. Wong will also examine the recent genomic sequencing of primary human small cell lung cancer samples and try to determine if there are additional mutations that that should be modeled in the mouse.
Notable Accomplishments
Dr. Wong and his colleagues have published two papers, in Cancer Research and Nature, including work supported by UALC.
Update 10/2021: Targeting HER2 Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib, Cancer Research