With over 2 million new cases diagnosed in 2018, breast cancer remains the most commonly occurring cancer in women and the second most common cancer overall. Survival rates vary greatly worldwide, ranging from 80% in North America, Sweden and Japan to around 60% in middle-income countries and below 40% in low-income countries (Coleman et al., 2008).
Despite considerable progress in treatment modalities, breast cancer patients die from cancer dissemination and metastases. Current understanding of the underlying processes that allow cancer cells to circulate in the bloodstream and invade and colonize in other organs is limited. Expanding the body of knowledge on these processes is one of our areas of focus.
Immunotherapy is a new modality which has revolutionized the treatment of cancer for multiple types of tumors. However, breast cancer has shown only modest benefit from immunomodulatory therapies, if at al. This is principally due to tumor escape mechanisms. We have only limited understanding of these mechanisms. Our focus on translational research aims to better understand these resistant mechanisms, broaden current clinical applications and overcome some of these unsolved issues.
The research laboratory is located within the campus of the Rabin Medical Center, thereby enabling us to benefit from a fruitful multidisciplinary collaboration with the oncology and, surgery and pathology institutes and facilitating access to patient tissues and blood specimens. This advantage allows us to perform in-vitro, in-vivo and ex-vivo experiments that more closely mimic clinical conditions of breast cancer.
Research Projects in the lab.
- Elucidation of molecular drivers of the breast cancer metastatic cascade to reveal new biomarkers for clinical translation:
One of the molecular mechanisms studied in our laboratory is the endoplasmic reticulum stress response which is activated in tumor cells and breast cancer leucocytes by commonly used chemotherapy agents for these patients. Our study suggests a different approach to treat metastatic breast cancer. We believe that conventional chemotherapy could be combined with therapies that regulate the unfolding protein response (UPR), a cellular stress response related to the endoplasmic reticulum stress.
- Discovery and study of a novel tumor escape mechanism and its reversal by a peptide which binds to an unconventional immunotherapy target.
Monoclonal antibodies directed against immune checkpoints, e.g., the programmed cell death protein 1 or programmed cell death ligand 1 (PD1/PDL-1), in or without combination with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), have been successfully used for the treatment of different cancer types. In general, immunotherapy has shown only very modest benefit in breast cancer patients.
Related to this research, we revealed a heretofore unpublished tumor escape mechanism. We found that breast cancer inhibits the Src family of tyrosine kinases, resulting in the suppression of immune cells. We are studying a novel molecular mechanism of an immune modulating therapeutic peptide (C24D) that reverses the tumor escape mechanism through the CD45 signaling pathway. We aim to develop a new platform of immuno-oncology drugs for the treatment of breast cancer based on C24D and the CD45 signaling pathway.