The first step towards designing new cancer drugs
Researchers co-led by scientists from the University of Kent (Canterbury, UK) and Goethe University (Frankfurt, Germany) have identified a first step in the design of a new generation of anti-cancer therapeutics.
Novel research from a group co-led by the University of Kent (Canterbury, UK) and Goethe University (Frankfurt, Germany) has identified the first step towards designing and producing a new class of anti-cancer drugs, information that could lead to more tailored therapy for patients suffering from drug-resistant cancers.
The majority of anti-cancer therapies fail due to drug resistance, and as such it is a major cause of patient deaths despite the strides made in cancer treatment in recent decades. Cures are in general achieved by early detection of cancer, followed by localized therapy with a combination of surgery and radiotherapy, with the prognosis grim once cancer cells have travelled through the body and formed secondary tumors (metastases).
Effective systemic drug therapies are therefore urgently needed to treat metastatic disease, but many cancers are characterized by intrinsic or acquired resistance. One of the most significant resistance mechanisms in cancer cells is the action of ATP-binding cassette (ABC) transporters, which act to move anti-cancer drugs from cancerous cells.
Of these, ABCB1 is the most relevant, and previous attempts to target it with therapeutics have failed, in large because ABCB1 is expressed throughout the body, particularly at tissue barriers such as the gastro-intestinal barrier and the blood brain barrier. Any targeted therapeutics have therefore resulted in toxic side-effects, affecting the body distribution of other molecules such as drugs and food constituents.
This novel research demonstrates that certain ABCB1 inhibitors specifically interfere with ABCB1-mediated transport of some anti-cancer drugs, providing a first step toward designing combinations of anti-cancer drugs and ABCB1 inhibitors. These future combination therapies could, in theory, cause the accumulation of cancer drugs in cancer cells without affecting the body distribution of other key molecules, providing hope for metastatic disease.
Source:Michaelis M, Rothweiler F, Wuglics M et al. Substrate-specific effects of pirinixic acid derivatives on ABCB1-mediated drug transport. Oncotarget, 7(10), 11664-11676 (2016); https://www.sciencedaily.com/releases/2016/03/160309124753.htm