Hepatocellular carcinoma is one of the most common cancers worldwide. The problem with treating this hepatocellular carcinoma is that the tumor quickly finds ways to adapt and becomes resistant to chemotherapy drugs. Researchers in Graz are looking for ways to promote or strengthen the response to therapy in HCC. Last has a team around Andrew Prokesch from the Gottfried Schatz Research Center investigated whether fasting could have a supportive effect on cancer therapy. Which they have now published in the journal Science Advances results are promising, said the Med-Uni Graz in a broadcast.
Fasting for cell renewal
The importance of fasting has changed significantly in recent years. While for a long time it was primarily a religious and esoteric topic, it has also been scientifically examined more closely in recent years and the positive effects of regularly not eating are clarified in studies. It turns out that, in addition to weight loss, it is above all the change in metabolism that has a positive effect through fasting.
At Med-Uni Graz, Andreas Prokesch from the Chair of Cell Biology, Histology and Embryology is investigating fasting at the cellular level: Among other things, his team is concentrating on the extent to which nutrient deprivation influences the mechanisms of reprogramming gene regulation. Among other things, the function of the transcription factor and tumor suppressor p53, which seems to play an important role in various metabolic organs (such as liver and adipose tissue), is being investigated. A possible application of this is to use the activation of this tumor suppressor by fasting as an adjunct to cancer therapy.
Hope: Targeted treatment
Most recently, the researchers, in collaboration with the University of Utrecht and the Max Planck Institute in Dresden, researched the molecular and metabolic processes during the treatment of cancer cells of the hepatocellular carcinoma. The targeted therapy of cancer with the fight against individual or a few target structures on or in malignant cells has given rise to hope in recent years, but it has been shown that these drugs also lose their effectiveness over time. The Graz researchers suspect that the changes in the cell caused by fasting can help to circumvent these resistances.
The research team tested whether starvation can increase the effect of sorafenib in treatment-resistant HCC. It was previously known that the active ingredient, which is used against hepatocellular and renal cell carcinomas, among other things, disrupts cell division and cuts off the blood supply to tumors, tumor cells are prevented from multiplying, and newly formed cells can no longer connect to the vascular system will.
As the researchers at Med-Uni Graz were able to show, sorafenib has another effect that also plays a role in resistant cells: it inhibits the cellular respiration of the mitochondria. However, if sufficient glucose is available as an energy carrier, the cancer cells can still continue to divide. “However, if sorafenib is used together with fasting – and thus restriction of glucose – the two most important energy-supplying mechanisms are suppressed and tumor growth is significantly slowed down. Fasting can thus help to prevent or reduce the development of resistance to sorafenib,” summarized Prokesch.
The study examined the effects of sorafenib and fasting in isolated liver cancer cells, in organoids obtained from patients, and in the live organism of mice. The publication also showed that the tumor suppressor p53 is necessary for the combinatorial effect of fasting and sorafenib. This treatment strategy is therefore an option for the two-thirds of all liver cancer patients who do not have a p53 mutation. Further studies will investigate whether this combination therapy can be transferred to the treatment of hepatocellular carcinoma in clinical practice.