Risk Monitoring


Personalized medicine’s molecular approaches cannot only be used to detect risks as detailed in the last blog entry, but may also help to monitor risks throughout therapies or in case a substantial risk has been detected. 


I will focus on two aspects of truly personalized molecular risk monitoring which is DNA and RNA analysis. Of course there are many more monitoring approaches using all kinds of biomarkers or metabolite screenings to follow how patients fare during or after treatments, but those are usually not really personalized. 


Tumor typing 


One molecular approach is tumor typing which is applied not only to solid tumors but especially to leukemias. This is done by repeatedly taking samples (blood samples) to detect newly arisen mutations. These mutations might or will cause a drug resistance in a tumor or in case of a period free of disease progression (remission) the end of such peaceful times. As illustrated in Fig. 10, regular tumor typing can detect new variants before they take over and cause massive problems. Leukemia types A - D are not  indicative of different leukemias but are used to differentiate different mutations within the leukemic cell population. This also helps to determine which drug might be the most efficient way to battle the new variant. This way it might be possible to keep patients in a remission or to conquer the new (maybe more aggressive) type of a tumor or leukemia before it has multiplied out of control. Lower dosage and less side effects are some of the immediate benefits for the patient. Targeted treatments and avoiding unnecessary treatments during a remission are other benefits of such monitoring efforts. 


Figure 10: Monitoring of the genetic variants in a leukemia for early detection of new threats


Early warning for metastasis


Metastatic tumors send their nascent metastases through the blood stream to other parts of the body, where they can start new local tumor growth (e.g. in the liver) causing problems later on as they grow and destroy healthy tissues. This is often also accompanied by the occurrence of additional mutations in the circulating tumor cells which can be detected in blood samples as well. Actually, the detection of tumor cells in the blood even from solid tumors elsewhere in the body is behind the term liquid biopsy, because information about the tumor can be derived almost as if a real biopsy of the tumor tissue would be available. 


RNA expression precedes changes in tumor nature and growth


In order to affect the body and support growth every cell has to transcribe genetic information into RNA (and later translate that into proteins). In many cases there is a correlation (not necessarily 1:1) between changes in RNA levels and subsequent changes in protein levels and cell behavior. The advantage is that the increase in the levels of multiple RNAs usually also precedes pathological effects which might result from such changes. Again an advanced warning that things are changing. Such changes are not necessarily coupled with genetic changes - detected by tumor typing - but may result from environmental changes or drug treatments. This might confirm beneficial changes (disappearing growth single cascades) or indicate tumors reverting to their bad old habits of uncontrolled growth. 


Risk monitoring by molecular analysis of DNA and RNA always require at least a blood sample and thus a trip to the MD’s surgery. However, this inconvenience is more than balanced by the advanced notice of changes before they become clinically manifest, especially as such molecular monitoring is only applied to patients with a known problem and not for a general screening of populations. This is a major difference to the risk detection which is really suitable for large-scale screening (e.g. with newborns). 


What’s coming up next?


Next week will focus on a few explanations why side effects are inevitable and how they arise