Is screening for mutations in cancer not effective enough?

Recently, the issue of finding mutations associated with various forms of cancer has attracted a lot of attention, says Eric Topol, editor-in-chief of the Medscape Internet portal. On the one hand, for many years only screening methods that detect individual mutations have been available to us. If someone was diagnosed with colon cancer, they were screened for KRAS mutations, and for breast cancer - for HER2 mutations. However, very serious changes are taking place now, and we are beginning to recognize that all this is impractical in general. The question is in which direction we will move further.

According to data published in the journal Nature Biotechnology, one of the recently validated tools is a limited exome panel containing 287 genes involved in the development of cancer. It was created by Foundation Medicine and involves the transfer of formalin-fixed and paraffin-filled tumor tissue samples obtained during biopsy to the company's laboratory located in Cambridge, Massachusetts. There, specialists conduct highly sensitive DNA sequencing. The company's specialists do not consider anything other than these 287 coding elements, but we know that many more components are involved in the development of cancer than this small fragment of the genome.

Nevertheless, the results obtained are very interesting. The company claims that mutations, presumably the root cause of the appearance of the tumor, can be found in almost 80% of patients. This does not bode well for centers scattered across the country that do not practice sending samples for sequencing.

Of course, there are other solutions to the problem, which consist in the ability to evaluate not only 287 genes. What about the entire exome consisting of 20,000 genes? What about the whole genome? More recently, thanks to the new analytical tool FunSeq, we learned about such things as the promoters of the TERT genes – long non-coding segments involved in the development of aggressive prostate cancer, as well as that more than 100 non-coding sequences located at a decent distance from the genes can trigger the progression of malignant tumors.

We have methods that allow us to understand the emerging information about oncogenes and tumor suppressor genes involved in the early stages of tumor formation. Over the past 2 years, the U.S. Food and Drug Administration has approved 20 new drugs designed to treat tumors whose DNA contains certain mutations. However, unfortunately, we do not currently conduct extensive screening of patients. We need to mobilize and come up with new solutions based on the unusually large amount of information at our disposal about the genomics of cancer and the causes of the development of this disease, which would allow us to solve patients' problems more effectively.

And the last moment. Today we can choose a drug, often very expensive, specific to a particular mutation. Its use can provide an extraordinary effect that can last for 9-12 months. However, after that, as a rule, the disease recurs.

We should take a more rational approach to new combined therapies, highly sensitive sequencing and finding out the possibilities of using extracellular tumor DNA or other methods. At the same time, it is necessary to take into account the exceptional heterogeneity of tumors, which will allow assessing their resistance and the likelihood of recurrence. This is the next stage in the development of antitumor therapy, which we need to comprehensively evaluate.

As you can see, the choice of optimal approaches to the use in routine medical practice of the knowledge we have gained in the field of cancer genomics is a very ambiguous problem.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Medscape materials:
Topol: Cancer Mutation Screening 'Grossly Insufficient'.

Portal "Eternal youth" http://vechnayamolodost.ru27.11.2013