Survival of cellular stresses including hypoxia, oncogene expression, rapid proliferation, genomic instability, and chemotherapeutic insult is a hallmark of cancer. Without specific stress response proteins, tumors cannot survive these limitations. Upon activation of the stress response, a central regulator of cell stress survival that we have identified (CRR9) translocates to the tumor cell surface and activation of multiple independent survival signaling pathways occurs. Expression of this stress response protein is necessary for KRas- and other oncogene-driven tumors to form. CRR9 plays a critical role in tumor initiation, progression, and resistance to therapy.
Monoclonal antibody CRR9 antagonists:
We have systematically developed biologics, including a panel of monoclonal antibodies targeting the extracellular domain of the tumor stress response protein CRR9. Lead antibodies (ESS102) inhibit surface accumulation of the protein, leading to decreased survival signaling, decreased anchorage-independent growth, and most importantly, use of our proprietary antibodies in preclinical animal xenograft models results in tumor regression. Learn more about CRR9 as a therapeutic target HERE.
RNA inhibition and Genetic Approaches:
We are developing RNAi-based therapeutics capable of decreasing accumulation of proteins in this pathway. Pre-clinical testing using animal xenograft models of cancer reveals that this approach also effectively decreases accumulation of the target protein, sensitizes tumor to chemotherapeutics and decreases tumor formation itself. Our multi-faceted approach and pipeline ensures effective targeting of this key regulator of the stress response.
Above: Lung tumor formation caused by the KRas oncogene in mice is prevented by inhibition of CRR9.
Diagnostics & Biomarkers:
We have demonstrated overexpression of proteins involved in our target pathway in most tumors tested and their alteration in response to therapy. We are currently developing solutions to serially monitor expression of these markers non-invasively from patient serum. Preliminary data suggests that these may be important biomarkers that could have a role in guiding therapy decisions, developing prognosis, and monitoring response to treatment.
Essential Biotechnology LLC’s therapeutics target a novel mechanism of tumor survival, growth, and progression that is highly effective and synergistic with existing therapies. Sensitization to existing drugs will reduce the necessary dose and toxicity associated with these therapies. Decreased morbidity, metastasis, and toxicity will result in decreased medical costs and increased quality of life.
Companion diagnostics and theranostics under development may guide therapy while also providing prognostic information for patients. These diagnostics include circulating markers as well as protein markers in excised or biopsied tumor tissue. Evidence suggests that our circulating marker, which is detectable with our proprietary biologics, may also serve as an early marker of cancers, including ovarian, pancreatic and lung adenocarcinomas potentially speeding cancer detection and improving patient outcomes.
A granted US patent and pending international patents protect these assets.
Essential Biotechnology is the leader in this field and continues to conduct seminal research that will redefine the way that cellular stress response elements such as CRR9 are targeted for therapeutic benefit in patients.