Technologies

Background

CARP-1 (Cell cycle and apoptosis regulator protein) is a regulator of cell growth signaling.

The researchers have found that CARP-1 inhibits cell growth by binding with the anaphase promoting complex (APC)-2 protein. Since breast cancers often have dysregulated cell cycle signaling, the researchers hypothesize that CARP-1 mimetics that target APC-2/cell cycle signaling will inhibit HBC cell survival pathways. The researchers’ work has shown that CARP-1 is a regulator of apoptosis induced when proliferation signaling by epidermal growth factor receptor (EGFR) is inhibited. The EGFR family of proteins is a known risk factor for development of disease, predictors of prognosis and response to therapy, and is utilized as therapeutic targets against a variety of cancers including breast cancer. CARP-1 mimetics are anticipated to facilitate effective targeting of key oncogenes (APC-2) and will serve as efficacious anti-tumor agents for treatment of breast cancer alone or in conjunction with chemotherapy agents such as Adriamycin, Herceptin, Iressa, Lapatinib, and Erbitux. The researchers hypothesize that CARP-1 is a novel suppressor of HBC growth and is a key regulator of Adriamycin as well as EGFR signaling pathways. CARP-1 mimetics have the potential to sensitize chemotherapy-resistant cancers for growth inhibition. Thus, a combination of CFMs and agents like Adriamycin or Herceptin is anticipated to be superior in inhibition/killing of diverse phenotypes of breast cancer, including the drug-resistant cancers. The researchers want to develop novel, cell permeable small molecule mimetics of CARP-1 function for efficient and safe targeting of breast cancers by exploiting cell growth inhibitory targeting of APC-2 proteins by CARP-1.

Technology

The innovation and challenge of the approach was to identify molecules that mimic CARP-1 function and were capable of inhibiting oncogenic signaling by the APC cyclosome pathway. Since an oncogene is required for survival of cancer cells, targeting of the oncogene pathway by CARP-1 mimetics will exploit the Achilles heel of cancer. The APC cyclosome pathway is a crucial regulator of cell cycle progression and various cell cycle check-point controls are often compromised in a range of cancers, including the breast carcinomas. The APC-ubiquitin ligase complex is a hotly pursued target for therapeutic intervention in cancers. A chemical library of over 10,000 compounds was screened and three were selected.