Guardant 360 is basically a liquid tumour Biopsy, so it’s aim is to pick up genetic mutations within the body that are excreted by the tumour. If you are wondering why this is important, it’s because the more detailed understanding of the tumours genetic profile, leads to hopefully better or more accurate treatments (immunotherapy, chemotherapy), often with fewer or easier side effects. It provides a comprehensive genetic profile from 2 vials of blood, in approximately 14 days, this prevents the need for another actual tumour sample, so a liver biopsy in my case. Which is the reason we are now going down this route as my first liver biopsy only contained dead tumour tissue, which meant no genetic sequencing could take place, we may have to revisit this in the future.
Guardant 360 was pretty simple and due to Covid, we didn’t make the trip to London for it instead they sent it by Fedex down to Addenbrookes, where we took 2 vials of blood as far from last treatment as possible so on the day of my 100th round of chemotherapy (FOLFIRI and Cetuximab). We then placed this in a box with temperature controlled packaging and fedex took it back to London where i believe it is sent to USA for analysis.
This would have been the only tumour testing i have had other than KRAS (explained below) testing right at the beginning which came came back KRAS wildtype which is basically negative, no sign of a KRAS mutation. This meant that i qualified for Cetuximab as the likelihood of this being beneficial was high (thankfully for me I got a good stretch out of Cetuximab and did a lot to control/stabilise my early disease). Now in 2020 to qualify for Cetuximab you have to test for KRAS and BRAF (explained below), so i haven’t had a BRAF testing this is going to be undertaken at the same time but i presume this will also be negative due to my response to cetuximab. Other than that i do not have a clue about any of my genetic sequencing and it sounds like an absolute minefield, but one i may have to begin to get my head around in order to keep searching for the next drug option if there is one.
KRAS GENE – The KRAS gene provides instructions for making a protein called K-Ras, part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell’s nucleus. These signals instruct the cell to grow and divide (proliferate) or to mature and take on specialised functions (differentiate). KRAS mutation within bowel cancer has been associated with poorer survival rates and increased tumour agressiveness and often resistance to certain treatment strategies.
BRAF GENE – The B-Raf protein is involved in sending signals inside cells which are involved in directing cell growth. BRAF is a kinase, a protein that sticks chemical ‘tags’ onto other proteins, activating them in order to pass on signals in the cell. As you might expect, faults in BRAF can have big implications for cells – and for cancer.
As i said, within 2 weeks the results came back with a genetic breakdown of at least 74 genomes. When it arrived was very confusing and hard to understand unless you knew all the gene names and the effect of those being negative or positive.
However, a few bits were highlighted and one of them was KRAS gene, previously wild type, this was now positive. This is a bit of a game changer and means a big switch up in treatment needed as this means Cetuximab (EFGR Inhibitor) will not work.
Over time my tumours have acquired mechanisms of resistance to Cetuximab. Little tumours found a defence basically to the current weapon we were using so now we need to try and attack the army of tumours from a different angle and with some new armoury. This new armoury is going to be Avastin as Avastin is NOT an EFGR inhibitor it is a VEGF inhibitor.
EFGR Inhibitor “blocks the activity of a protein called epidermal growth factor receptor (EGFR). EGFR is found on the surface of some normal cells and is involved in cell growth. It may also be found at high levels on some types of cancer cells, which causes these cells to grow and divide. Blocking EGFR may keep cancer cells from growing.”
VEGF inhibitor works “by slowing the growth of new blood vessels by inhibiting vascular endothelial growth factor A (VEGF-A), in other words anti–VEGF therapy”
So time to give Avastin a shot and see what happens regarding the KRAS mutation once it has had a ‘drug holiday’ from Cetuximab. Overall the Guardant 360 seems to have come at the right time, without continuing with Cetuximab for another 6 rounds before finding out it wasn’t working.
Onwards to Avastin we go!!