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

IN THE NEWS: McLaren Greater Lansing program helping people quit smoking for good

WILX If your new year's resolution is to quit smoking, it's not too late to get started. The Freedom From Smoking program, held at the Karmanos Ca...

Read More

IN THE NEWS: You're Not Crazy. You Just Have Cancer. The Importance of Behavioral Health Therapy During Cancer Treatment

Coping with Cancer Felicity Harper, Ph.D. , clinical psychologist and member of the Supportive Oncology Multidisciplinary Team at Karmanos, author...

Read More

Genetic counseling now offered at Karmanos’ northern Ohio cancer center

The Barbara Ann Karmanos Cancer Institute now offers genetic counseling services at the Karmanos Cancer Institute at The Toledo Clinic Cancer Cent...

Read More
News

Cancer death rate decreases by a third | WJR’s The Guy Gordon Show

Listen Now

WebMD Health Discovered – The Fight for Equity in Multiple Myeloma Care

Listen Now

ASCO Education – Impact of Implicit Racial Bias on Oncology Patient Care and Outcomes

Listen Now