The LBMCC has been studying molecules from plants (Zanthoxylum fagara, left), a marine sponge (Aplysina aerophoba, top right) and pre-existing drugs as new potential cancer treatments. (Courtesy of Pixabay.com, Di Yoruno - Opera propria, CC BY-SA 3.0 & Wikipedia, CC BY 2.0).
New treatments from old molecules – looking back at 2016.
Cancer can affect organs and tissues in the body with differing symptoms. But when we look at what's going on inside a cancer cell several common processes are occurring. These molecular similarities include machinery used by the cancer cell to allow its uncontrolled growth and replication. In many cases, there are genetic switches that, if turned on or off, favor the overproduction of cancer cells leading to tumors.
Prof. Diederich’s teams at the College of Pharmacy of Seoul National University (SNU) in concert with LBMCC in Luxembourg have been looking at these molecular similarities; working hard to identify natural compounds that could be used to target them and attack cancer. Each patient can be affected slightly differently, and so finding the best target for each patient is key to improving the effectiveness of drugs.
In early 2016, the LBMCC published a paper identifying two molecules like those found in plants such as wild lime (also known as Zanthoxylum fagara) with the potential to treat prostate cancer. They found that these molecules can interact with both DNA and other cellular components to prevent tumor growth. The team also ran large-scale screening of other potential molecules to test for their efficiency in attacking leukemia cells. In doing so, another natural molecule was found to be effective; isofistulatin-3, extracted from a sea sponge (Aplysina aerophoba).
Reviewing the year with Prof. Marc Diederich.
The molecules identified in both those early studies were tested using cell lines that mimic cancer behavior. Prof. Diederich and his team decided to take this research to the next level and managed to obtain cancer cells taken from patients of the Oncopole in Toulouse. In their latest publication in Leukemia, released in November, researchers from the LBMCC/SNU developed a combination of two pre-existing drugs (UNBS1450 and Venetoclax) for treatment of acute myeloid leukemia. With success, they found the mix particularly effective in obliterating cancer cells taken from patients with a specific gene mutation – hence the term personalized.
In his opinion, Prof. Diederich considers this latest publication in Leukemia to be their biggest success of 2016. He holds that particular segment of their research in such high esteem because “Venetoclax is a hot topic at the moment and our findings were validated by samples taken from existing patients”. If the treatments work in real cancer cells, then their effectiveness as cancer medications of the future is ever the more likely.
What can we expect from the LBMCC in 2017?
It seems clear that moving forwards means getting these treatments tested in human models. Although, Diederich is predicting difficulties, “we are getting to the point where we will need to set up a clinical trial … but that will require sufficient funding”. If Prof. Diederich and his team are to succeed, then they will need to continue evolving and collaborating with labs (such as the Oncopole in Toulouse or Seoul National University’s Children’s Hospital) that have access to the valuable patient samples required.
They do have another trick up their sleeve, however. Diederich is planning on developing their use of a technique known as patient-derived zebrafish xenograft. In short, the technique allows cells taken from a patient’s tumor to be transplanted into a simple animal model, the zebrafish. This exciting, novel technique has proven useful for testing which treatments could be most effective in specific patients. By using xenografts in this way, they could also provide a technique to predict the outcomes of different treatments and therefore tailor the treatment to the individual.
New techniques such as “patient-derived zebrafish xenograft” will be used in the coming year to transplant patient cancer cells into zebrafish for study – as pictured here. In red, the transplanted cancer cells. (Courtesy of Prof. Marc Diederich, LBMCC).
Cancer is such a complex disease that seems to be able to fight back with each step research takes towards a cure. The findings coming out of the LBMCC lab in 2016 join the ranks of world-class cancer research. Over the year to come, we can hope to see more trials on cells taken from patients, bringing us even closer to personalized cancer treatment.