Our laboratory focuses on elucidating the molecular mechanisms of cancer therapeutics, drug resistance, and metastasis mainly in breast cancer. We are also interested in developing and pre-clinical testing of novel anti-cancer therapeutics that are easily translatable to clinics.
We conduct interdisciplinary research by combining our expertise in cancer cell biology, high-throughput functional transcriptomics/proteomics and drug discovery, with those of the experts from the medicinal chemistry, bioinformatics, and medical oncology fields to target the most aggressive cancers.
In this line, we develop and utilize state-of-the-art tools, e.g., cancer cell lines sensitive or resistant to various standard of care therapies developed in our lab, patient-derived xenografts (PDXs), transgenic animal models, organoids (both PDX- and patient-derived), and patient tumor tissues to answer key questions in drug resistance and metastasis.
Results of our cutting-edge research:
We recently identified transforming acidic coiled-coil 3 (TACC3) to be a key protein for the growth of highly aggressive, centrosome amplified cancers (Saatci et al, Cell Death and Differentiation, 2023) and developed a highly potent, novel inhibitor of TACC3 as an anti-cancer agent (patent: WO/2020/018039 and Akbulut et al, Molecular Cancer Therapeutics, 2020). We completed the lead optimization of this inhibitor in collaboration with pharma which got the FDA IND approval for the clinical tests in cancer patients. We are currently studying the role of TACC3 in several different cancer-related processes using both the state-of-the-art tools and the first-in-class TACC3 inhibitor.
We have also uncovered the roles of the extracellular matrix (ECM) re-modeler protein lysyl oxidase (LOX) in chemotherapy resistance in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype (Saatci et al, Nature Communications, 2020). We recently developed a novel, highly potent, and safe inhibitor of LOX with excellent drug-like properties (Cetin-Saatci et al, Cell Chemical Biology, 2024). We are studying the non-canonical roles of LOX in tumor progression in different cancers.
We have also long-term interest in elucidating the mechanisms of endocrine resistance and metastasis in ER+ breast cancer and identifying druggable targets to overcome resistance and inhibit metastasis. We recently showed that targeting phosphodiesterase 4D (PDE4D) induces toxic PARP trapping upon cAMP-induced DNA damage and reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer (Saatci et al, Nature Communications, 2023). We are currently studying the role of other proteins in resistance to both endocrine and CDK4/6 inhibitors.
Research Topics: Breast cancer therapy, Drug resistance and metastasis, Tumor microenvironment, Signaling pathways, Drug discovery