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New Small Molecule Compounds for the Therapy of Metastatic Breast Cancer

Project Team

Alessandro Fatatis, MD, PhD, Professor of Pharmacology, Physiology and Pathology. DUCoM Co-Leader, Program in Prostate Cancer, Sidney Kimmel Cancer Center, TJU.

Joseph Salvino, PhD, Professor of Pharmacology and Physiology, DUCoM.

Olimpia Meucci, MD, PhD, Professor and Chair. Department of Pharmacology and Physiology. Deputy Director of the Clinical and Translational Research Institute, DUCoM.

Wm Kevin Kelly, DO, Professor of Medical Oncology and Director of the Division of Solid Tumors, TJU.

Abstract

Despite the successful management of localized breast cancer by surgery and radiotherapy, more than 20% of patients will eventually present with distant metastases. Metastatic disease is the main cause of death for breast cancer patients and is currently incurable.

We have revealed the crucial role of the chemokine receptor CX3CR1 in regulating the seeding and growth of breast cancer cells to skeleton and soft-tissue organs. Building on this evidence, we have synthesized novel, potent and selective small-molecule antagonists to target CX3CR1 and have provided pre-clinical validation of their activity in animal models with high translational relevance.

Our program is focused on delivering an orally available drug to therapy with the intended use in patients with metastatic disease to arrest or decelerate the clinical progression and – in combination with standard of care – also improve the treatment of the existing metastatic lesions. Clinical proof of principle will be obtained in phase-Ib and phase-II clinical studies on patients with Inflammatory Breast Cancer (IBC), as this tumor progresses dramatically faster than adenomarcinoma, allows for breakthrough therapy designation and circumvents the major hindrance of lengthy and expensive trials that has historically undermined the development of effective anti-metastatic therapies with curative intent.