Understanding treatment resistance tumor evolution through allele-specific genomic analysis
by
Francesca Demichelis(Centre for Integrative Biology, Università di Trento)
→
Europe/Rome
Aula Conversi (Dipartimento di Fisica - Ed. G.Marconi)
Aula Conversi
Dipartimento di Fisica - Ed. G.Marconi
Description
Understanding treatment resistance is emerging as a
critical hurdle for precision medicine in cancer care. We
exploit single base resolution data and allele-specific analysis
to reconstruct tumor evolution charts and to quantify intra- and
inter-tumor molecular heterogeneity. These approaches proved
useful in identifying potential mechanisms of resistance to AR
(androgen receptor) directed therapies in prostate cancer.
Specifically, we found evidence of the emergence of an
alternative AR-indifferent cell state through dive! rgent
clonal evolution as a mechanism of treatment resistance in
advanced prostate cancer. Through serial plasma samples
analyses, we then delineated patients tumor dynamics during
AR-directed therapy and nominated a biomarker predictive of
treatment response.