The Pros and Cons of Personalized Medicine

DWIH NY: To begin, tell us about your research and what recent advancements you have seen emerge in the field of genomics and personalized medicine.

Yaspo: I am working in the fields of cancer genomics and precision medicine, using systems biology approaches to understand the tumor molecular landscapes in their complexity rather than focusing only on driver mutations. We have contributed this type of global analysis using the transcriptome in particular in several solid tumors (colon cancer, prostate cancer, medulloblastoma) in the framework of Innovative Medicine Initiatives and ICGC projects. We have also a particular interest in pediatric leukemias, relapse ALL and AML, partnering with several clinical units to identify novel oncogenic targets and therapeutic vulnerabilities.

One development now emerging is the notion that the multiple molecular mechanisms which cooperate to re-program normal cells into threatening oncogenic warriors cannot be detected at the DNA level only reading out mutation profiles.

DWIH NY: Oh, how cool! So some of our fiercest warriors in the fight against cancer are rogue, undercover agents.

Yaspo: Much more is out there, too, including epigenetic reprograming of gene activity for instance. Seminal advances have also been witnessed with studies demonstrating the key relevance of interactions between tumor cells and their microenvironment and the boom of immune checkpoint inhibitors. Predicting disease outcome in the field of cancer is another very relevant aspect which has emerged from a number of integrative molecular studies.

DWIH NY: What are the biggest challenges facing those in the scientific community developing novel clinical oncology practices?

Yaspo: I think that although the technology is there (e.g NGS, or next generation sequencing, for exome and transcriptome instance), there is still some way to go regarding acceptance of novel technologies (even if not that novel in fact), including the analysis of more complex data as compared to panel sequencing for instance. Further, there are limited competences in many clinical centers to analyze this type of data, which then prompts the need to build strong partnerships. This is a new modus operandi that is not easy to implement in a classical environment not always prepared to introduce drastic changes or partial share of responsibilities.

DWIH NY: Pave the way for the future, we like to say. We’ve titled this issue of our news “Pros and Cons of Precision Medicine.” In your opinion, are there any cons or risks in taking this novel more personalized approach in medicine and patient treatment?

Yaspo: In my opinion, there are less risks in adopting a more personalized approach than staying in the dark with very limited knowledge of the tumor molecular program. Of course, the challenge (and the risk) is that by tackling very individual molecular targets, there might not be a corresponding clinical trial in the classical definition, which would have evaluated the chosen (approved) drug in the particular context of each individual tumor. But on the other end, when all options have been tried and failed, what is the bigger risk ? trying or giving up ? I think that no one can tell here, not even what is more ethical. There are big challenges coming up in this direction. Further, it must be said clearly that by and large, clinical trials do not explore the global tumor molecular profiles, but rely on only one or a few markers, which is far too shallow to draw sound conclusions.

Evidently, cohorts in clinical trials are heterogenous in nature, but given that their molecular characterization is oversimplified, this complexity is basically ignored, which  might modulate the conclusions of the studies. The risk is also there to leave out the chance of identifying precise sub-populations of patients showing better responses or, in contrast, adverse effects. The notion of risk shall become an individual informed choice involving the patients and not only the clinicians.

DWIH NY: What effects has the pandemic had on personalized medicine and oncology?

Yaspo: Certainly, the overall focus has unavoidably shifted; the world wasn’t prepared for a pandemic and needs to push human and monetary resources there. But let’s hope this is temporary. The need of better care for cancer patients is as acute as before; the pandemic only makes it worse.

DWIH NY: Alacris Theranostics is a prime example of institutional research (from the Max Planck Institute for Molecular Genetics) leading to a practical application. Do you have any thoughts or tips for bridging the gap between scientific research and its applicability in the everyday practice of medicine?

Bridging the gap needs openness and to take more cooperative steps from both sides; the two worlds are still siloed in a sense. There is still a huge gap. It takes a bit of courage for researchers to advocate for new concepts in personalized medicine and a lot of time to actually get acceptance. If you look at it, the services currently offered in personalized medicine are far behind the huge potential of current technologies which could be implemented at a better cost. It might need a disruptive change in the health system, involving all stakeholders including insurances, establishing a balance of scientists and clinicians in evaluating and establishing applicable procedures. There are initiatives this direction, but things could move much faster.

DWIH NY: What can cancer research and genomics teach us about life?

Yaspo: One the one hand it teaches us that there is always much more to learn than what we know or discover, but we tend to forget this! On the other hand we need to comprehend and face the complexity of biological systems. Maybe it teaches us altogether to be more humble and courageous.

DWIH NY: A hard lesson! But a necessary one. Thanks for your time and contributions, Dr. Yaspo. Happy spring from New York.