Application of drug sensitivity screening in B-cell malignancies for informing precision medicine strategies
- Resource Type
- Authors
- Giliberto, Mariaserena
- Source
- Subject
- Language
- English
Cancer is still in many cases an incurable disease in urgent need for effective therapies and personalized treatment protocols. The work in this Thesis presents a drug sensitivity screening approach to test a number of anti-cancer drugs directly on cancer cells from patients with blood cancer. This identified possible treatment options and indicators of drug efficacy to assist clinical decisions on future individual treatment choices. In paper I differential drug sensitivities in multiple myeloma (MM) linked to corresponding in vivo clinical responses and synergistic drug combinations were identified. In the paper II results described the therapeutic efficacy of combined MEK/Bcl-2 inhibitors and provided a biomarker-guided combinatorial approach targeting MEK and Bcl-2 in B-cell malignancies. As part of paper III results described that both mutations in cancer-related genes and activity level of signaling proteins may serve as indicators of drug sensitivity or resistance in this model. We hope that this method may provide a clinically applicable drug-testing pipeline for patients with advanced disease and few remaining treatment options.