Molecular Therapeutics Theme 2 Accomplishments

Theme 2: Identify cellular/molecular determinants and clinically relevant biomarkers of treatment response on which to base therapy

Scientific Accomplishments 

Drs. Bepler, Gadgeel, A Schwartz, and Cote, working with Dr. Bollig-Fischer, identified “driver” mutations in non-small cell lung cancer (NSCLC) in African American and European American patients using the Sequenom MassArray system and a multiplexed panel for 214 oncogenic mutations in 26 genes previously identified in NSCLC. African Americans with NSCLC exhibited multiple genetic mutations more frequently than European Americans with a different mutation profile. These results provided impetus for CAP/CLIA certification of the Genomics Core in 2013 for use of custom panels for lung cancer oncogenes and amplifications/deletions.

  • Lead researchers - Drs. Bepler, Gadgeel, and Bollig-Fischer
  • Collaborative researchers - Drs. Schwartz and Cote

Dr. Ratnam, working with Drs. Gadgeel, Shields, Matherly, and Bepler, demonstrated the role of glucocorticoid receptor (GR) status as a determinant of the variability in the sensitivity of non-small cell lung cancer (NSCLC) cells to pemetrexed (PEM), a S-phase-targeted drug in front-line or maintenance therapy  of advanced NSCLC, generally administered with dexamethasone (Dex). Their results predict that in non-squamous NSCLC, S-phase suppression by Dex, combined with a reduction in PEM transport, attenuates responsiveness to PEM and that GR status is an important determinant of tumor variability of this response.  Based on these in vitro results, an investigator-initiated clinical trial (Shields, Lead PI; Ratnam, Gadgeel, Heilbrun, collaborators) is enrolling NSCLC patients who will be screened by RT-PCR for high levels of GRα, then imaged with FLT-PET to test the hypothesis that Dex will decrease S-phase progression, as reflected in decreased activity of thymidine kinase-1.

  • Lead researchers - Drs. Ratnam. Gadgeel, Shields, Matherly and Bepler.
  • Collaborative researcher - Dr. Heilbrun

The Latest From Karmanos Cancer Institute

News

Illuminating Lights, Beautiful Weather Brought Record Attendance to Sk8 to Elimin8 Cancer™ to Benefit Research at Karmanos

Sk8 to Elimin8 Cancer™ Detroit Celebration and Ice Show was another fantastic event this year, bringing out more spectators and raising more money...

Read More

A Precise Beam of Hope: Gamma Knife Procedure Gives Patient New Lease on Life

Paul Poole never expected his life would change in the blink of an eye. At 69 years old, he was enjoying his life in Redford with his wife of 32 y...

Read More

$1.4 Million Awarded to Karmanos, WSU Researcher to Expand Findings Surrounding Prostate Cancer

A team of researchers at the Barbara Ann Karmanos Cancer Institute and Wayne State University (WSU) were awarded a $1.4 million, three-year grant ...

Read More
News

Prostate Cancer Aware | The Genetic Risks for Prostate Cancer with Dr. Isaac Powell

Listen Now

WDET | New WSU study finds ‘music medicine’ can help cancer patients

Listen Now

Sunday Edition | Updates in stage III and IVA cervical cancer treatment

Listen Now