About Dr. Annette Khaled

Developing personalized treatments, harnessing nanomedicine and immunotherapy for metastatic cancers

The research interest of the Khaled lab is developing new cancer treatments, using cutting-edge nanotechnology and understanding the underlying changes that drive metastasis to discover new molecular targeted agents.

(1) A novel polymeric nanotechnology platform with imaging capabilities for targeted delivery of a therapeutic peptide

Death due to prostate cancer (PCa) generally results when patients develop metastatic castration-resistant prostate cancer (mCRPC). While current treatments for mCRPC improve survival, the disease still remains incurable, and treatments result in severe side effects. Therapeutic peptides, with cancer cell specific activity, are an especially promising treatment option for mCRPC. Recently, the Khaled lab discovered CT20p, a novel cytotoxic peptide that targets cancer-specific differences in the expression of a molecular chaperone. CT20p is a promising anti-metastatic agent because it causes detachment-induced cell death and impairs cancer cell migration. Using CT20p, our objective is to develop a targeted molecular nanotheranostic (dual therapy and diagnostic) platform that delivers the peptide in high concentrations to PCa and has the capacity for imaging peptide efficacy in murine models of PCa. To deliver CT20p to PCa, the peptide is encapsulated within novel hyperbranched polyester nanoparticles (HBPE-NPs) that are functionalized with polyglutamated folates, that natural ligand for a PCa-specific cell surface protein.

(2) Development of a Cytoskeletal-Disrupting Approach for the Treatment of Metastatic Breast Cancer.

Metastatic disease is a principal cause of death from breast cancer. There is a need to develop new anti-cancer agents specifically designed to target physiological aspects unique to cancer cells that spare normal tissue and can be tailored to individual patients. To this end, the Khaled lab discovered CT20p. The cancer-specific action of CT20p is based on its interaction and inhibition of a protein folding complex called chaperonin containing TCP-1 or CCT. Inhibiting CCT with CT20p compromises the cytoskeleton in breast cancer cells, which resulted in loss of cell adherence and migration, leading to cell death. The objective of our research is to investigate the levels of CCT and its client proteins in breast tumors and correlate results with susceptibility to CT20p to develop a personalized treatment approach for breast cancer. We hypothesize that CCT is a driver of carcinogenesis in the subgroup of breast cancer patients that develop late stage and disseminated disease and serves as a viable target for therapeutic intervention. Our work could yield a new personalized therapeutic strategy for breast cancer, for example, combining CT20p with immunotherapy like checkpoint blockage drugs, to eliminate drug-resistant cancer cells and prevent disease recurrence and metastasis.

Please visit my faculty website for moreĀ informationĀ and current publications.