Triple-negative breast cancer (TNBC) represents the most incurable and aggressive form of tumour in the breast. The absence of targeted therapies against this disease makes it accountable for more than half of all breast cancer-related deaths, or some 250’000 deaths world-wide annually. Overactivation of the Wnt signaling pathway through overproduction of Wnt ligands, receptor FZD7 and co-receptor LRP6 provides the growth-promoting signal in TNBC. As no drugs targeting this signaling pathway currently exist on the market, TNBC, as several other Wnt-dependent cancers, remains poorly treatable. A quest for Wnt-suppressing agents is in an urgent demand, and several approaches have been put forward to address this need. Among them is the development of specific antibodies and small molecule screening, actively pursued across academia and industry; these approaches are also utilized in the lab of the Swiss coapplicant Prof. Katanaev.
An alternative approach is represented by looking for novel anti-Wnt molecules from natural sources. In this regard, natural products from see hydrobionts is very attractive, as the chemical space such products occupy appears to be largely distinct both from that of medicinal plants and from that of the currently synthesizable small molecules. We will look for natural products from bacteria, fungi, and invertebrates from the South China Sea.
The Vietnamese co-applicant of the current proposal Prof. Long is the Head of the Institute of Natural Products Chemistry of the Vietnam Academy of Science and Technology, specializing on isolation and identification of bioactive compounds from marine organisms and their application in pharmaceutical, food, and cosmetics industries.
Through the combination of the expertise of the two co-applicants, novel molecules from hydrobionts and targeting the Wnt signaling pathway will be identified, their mode of action and molecular targets delineated, and the activity against TNBC and other cancer cells characterized. In the long-term, this endeavor will result in creation of several anti-cancer lead compounds. This current seed grant application will serve to lay the ground for the long-running drug discovery cooperation between the Swiss and Vietnamese partners.
Prof. Vladimir Katanaev
Prof. Pham Quoc Long