51IN - Targeting the BCL-2 pathway

Date 27 September 2014
Event ESMO 2014
Session Targeting signalling pathways in haematological malignancies: Are we close to the end of histopathological classification and the chemotherapy era?
Topics Drug Development
Haematologic Malignancies
Translational Research
Presenter Anthony Letai
Citation Annals of Oncology (2014) 25 (suppl_4): iv20-iv20. 10.1093/annonc/mdu301
Authors A. Letai, T.N. Chonghaile, L.J. Hogdal, P.D. Bhola, J. Montero, C. Touzeau, J. Ryan
  • Medical Oncology, Dana-Farber Cancer Institute, 02215-5450 - Boston/US

Abstract

Body

Abstract:

Many, if not most, anti-cancer agents kill cancer cells via the mitochondrial pathway of apoptosis. We have investigated ways that we can predict whether a particular agent will active apoptotic signaling on a personalized basis. We have found that we can predict response to conventional chemotherapy and to BCL-2 inhibition based on BH3 Profiling. BH3 Profiling is a functional assay that measures, on a single cell basis, mitochondrial sensitivity to BH3 peptides. As such, it can measure how primed a cell is to apoptosis. In a more recent application, we have combined BH3 Profiling with brief ex vivo exposures of patient cancer cells to drugs. We have found that this provides very specific information predicting whether an individuals cancer cells will respond to an individual agent. It can be mutliplexed so that many drugs can be simultaneously evaluated, even in combination. This approach, which we call Dynamic BH3 Profiling, can be applied as a personalization strategy for cancer patients. Most predictive biomarker approaches focus on the study of components of dead, non-functional cells. BH3 Profiling demonstrates the great amount of useful information that can be obtained by the study of strategic perturbations of functional cells.

Disclosure:

A. Letai: Dr. Letai has received fees for adviding AbbVie. Dr. Letai's laborotary has received funding to support research from AbbVie.

All other authors have declared no conflicts of interest.