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?

Chevron

BRAF, AN ORCHESTRATOR OF CELL DIVISION

The BRAF protein is involved in regulating cell division. It relays growth signals inside cells.

If the BRAF protein is dysfunctional, cell division can become chaotic and could bring about cancer.

Researchers have noted that the BRAF protein is altered in about 60% of melanomas, a certain kind of skin cancer.

Chevron

an infamous mutation

The BRAF protein does not function properly because of the following mutation:

nucleotide t is replaced by nucleotide a in the DNA sequence of the BRAF gene.

 

A NEEDLE IN A HAYSTACK...

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.

Chevron

Small cause, big effects

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.

Chevron

BRAF V600E: AN IDEAL TARGET

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.

VEMURAFENIB 

Vemurafenib was the first anticancer drug designed to target BRAF V600E, and was launched in 2011.

Much in the way a key is inserted into a lock, vemurafenib inserts itself into BRAF V600E.

When vemurafenib interacts with BRAF V600E, the mutated protein is inactivated. Result: the cancer cells die!

Vemurafenib has a greater affinity for BRAF V600E and consequently targets more the mutated proteins than it does the normal proteins, and thus the normal cells.

 

The importance of DNA profiling

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!

Chevron

BRAF V600E and other cancers

The BRAF V600E mutation is found in 60% of melanomas but also in the tumour cells of other types of cancer such as lung cancer.

Patients with lung cancer whose tumours reveal the presence of BRAF V600E can also benefit from treatments that include vemurafenib.

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.

Scroll Up