New therapeutic target for prostate cancer: Pro-protein convertase inhibitors

ISSUE ADDRESSED
Prostate cancer is the most common type of cancer in men. One in eight Canadians will be diagnosed with prostate cancer. Although the survival rate for men is high when the diagnosis is made early, a large proportion of patients with prostate cancer will develop resistance to currently available treatments, leading to a deterioration in their state of health. Thus, a new approach to treat this type of cancer must be considered.

TECHNOLOGY
The present discovery consists of new pro-protein convertase inhibitors blocking tumor progression by neutralizing the PACE4 enzyme. This revolutionary new approach specifically targets PACE4 in the proliferation pathway of prostate cancer cells. More specifically, targeting PACE4 synergizes the anti-tumor action, leading to cell dormancy via a blocked cell cycle and thus blocking angiogenesis and triggering the self-destruction of cancer cells.

ADVANTAGES
- In vitro, ex vivo and in vivo results have clearly established that PACE4 is a therapeutic target for prostate cancer.
- Inhibition of PACE4 has very powerful effects on the proliferation of cancer cells, even when they become resistant to antiadrogen treatment.
- Better survival rates are expected.

APPLICATIONS
- Therapeutic treatment for prostate cancer.
- Evidence that inhibitors are equally effective on breast and ovarian cancer cells.
- For diagnostics, possibility of using this approach as a tumor marker (prostate, ovary, breast, lung, pancreas, thyroid, testis and bladder).

INTELLECTUAL PROPERTY STATUS
Three patent families are related to the technologies
PACE4: MULTI-LEU PEPTIDES AND ANALOGUES THEREOF AS SELECTIVE PACE4 INHIBITORS AND EFFECTIVE ANTIPROLIFERATIVE AGENTS
- Turnover 2,727,574
- EP 2303910
- US 8658591
- US (Div) 9573974

STABLE PEPTIDE-BASED PACE4 INHIBITORS
- CA: 2846287
- EP: 2751141
- US: 9,809,621

SPLICED FORMS OF PACE4 FOR CANCER DIAGNOSTIC
- US (Provisional) 62/565276

PROOF OF CONCEPT

PACE4 levels are greatly increased in prostate cancer. (A) PACE4 mRNA levels in prostate tissue obtained from patients following surgery to remove the prostate. PACE4 mRNA levels correlate with level of disease severity. ANCT: non-cancerous adjacent tissue, Gleason 6-9 indicates the degree of severity. A higher Gleason indicates a more aggressive cancer and a poor prognosis. (B) Immunohistochemistry (IHC) of PACE4 protein in prostate cancer in comparison with normal tissues.

Project manager: Soraya Mahiout