An example of targeted chemotherapy

CLASSICAL CHEMOTHERAPY…

« Classical » chemotherapy targets cell division and therefore all the proteins involved in cell division, or indeed DNA itself.

Unfortunately, such treatments counter not only cancer cells but also healthy cells that are naturally fast-dividing. This causes side effects such as a decrease in white cells, hair loss or digestive troubles for instance.

… OR TARGETED CHEMOTHERAPY?

Targeted chemotherapy specifically attacks cancer cells by targeting exclusively the altered proteins particular to them.

Several cancers are caused by a mutation that is well-known in the world of precision medicine: BRAF V600E. If BRAF V600E is identified in a tumour, then the patient can be offered targeted chemotherapy. Why?

It was a question of finding 1 single mutated nucleotide among 3 billion… but most of all, making sure that this particular mutation is ONLY found in cancer cells and not in healthy cells!

Years of research were needed to find this mutation which is located on chromosome 7, on the BRAF gene. The first clues arose in the early years of the millennium.

The gtg → gag mutation changes the sequence of amino acids in the BRAF protein: one Valine (V) is replaced by one Glutamate (E) in position 600 of the BRAF protein sequence.

The mutation is written: BRAF V600E.

BRAF V600E mutation causes a change in the 3D structure of the BRAF protein. Result? The protein is permanently activated and cannot regulate cell division anymore.

Cell division becomes more rapid and anarchic, thus giving birth to a tumour.

The BRAF V600E mutation alters the 3D structure of the BRAF protein, and is only found in cancer cells.

The BRAF V600E protein is therefore an ideal candidate as an anticancer drug target.

Several drugs have been designed to insert themselves specifically in the modified site of the mutated protein to block its activity.

• Drug Design Workshop: BRAF

DNA profiling a patient’s tumour will help reveal whether the BRAF V600E mutation is present or not.

If the BRAF V600E is present, vemurafenib can be prescribed.

If it is not, then vemurafenib should not be prescribed!

• GLOSSARY
• Patient care
• What is DNA profiling?

ON THE IMPORTANCE OF UPDATING INFORMATION

All knowledge regarding BRAF V600E and its presence or absence in different types of cancer, is published in science journals and indexed in specialized databanks.

This particular knowledge is regularly updated, refined and corrected over time as scientific and technological advances are made (Example of disclaimer).

This type of knowledge – as are all types of knowledge regarding a particular tumour – is paramount in helping doctors find the best treatment possible for their patients.