When Dad entered his new GP’s office for a routine checkup, he never dreamed he would be walking into a cancer diagnosis.
“Your cholesterol’s a bit high” said doc, and sent a somewhat sheepish-looking Dad off for a CT scan to check that his arteries weren’t getting too furry. That’s when the mystery object on his liver was sighted, quite by accident. A whirlwind series of tests later, and a diagnosis was reached: Cancer with a capital C. Cancer of the colon, or colorectal cancer (CRC). Not the handy kind of CRC, the pain-in-the-butt kind (pun intended). A couple weeks later and we were given another letter: T for Terminal. Dad now had colon cancer that had metastasized (spread) to his liver, on which at least ten lesions had been spotted. Still reeling from the news, we were told that the type of cancer he had was unfortunately considered to be incurable and unlikely to respond well to chemotherapy. Just when it seemed like it couldn’t get any worse, however, a silver lining was revealed. His cancer was deficient in several mismatch repair proteins (more on these later), making him an excellent candidate for immunotherapy, a new(ish) contender on the cancer scene. The other C word (Cure) was even thrown in as a real possibility if the therapy was to work. What an emotional roller coaster we all were on!
P is for Pembrolizumab
Now for the science (the fun part). This bad boy (pictured below) is pembrolizumab (sold under the brand name Keytruda). Let’s call it P for short. It’s nothing like your traditional chemotherapy drug as it’s actually a complete protein and humanised antibody that is used to treat cancers such as melanoma, lung, and stomach, and, more recently, certain types of colon cancer.
How does it work? According to Wikipedia, P is a “therapeutic antibody that binds to and blocks PD-1 located on lymphocytes”. Let’s go over each of those terms:
Therapeutic antibody
This is a drug that uses antibodies, which are Y-shaped proteins that the immune system uses to identify and neutralise foreign objects such as viruses and bacteria. Antibodies interact with unique molecules displayed by the foreign object, called antigens, allowing them to recognise pathogens. Because each antibody can only recognise a single type of antigen, therapeutic antibodies can be tailored to target specific disease-related molecules associated with cancers and other diseases. These antibodies then stimulate a patient’s own immune system to attack the target cells.
PD-1
This stands for Programmed cell death protein 1, a scary sounding but necessary player that is responsible for ensuring the body doesn’t attack itself (i.e. autoimmunity). PD-1 is found on the surface of certain types of white blood cells (also known as lymphocytes) where it acts as an immune checkpoint to prevent the immune system from attacking cells indiscriminately. This is achieved through recognition of certain ligands (molecules) displayed on the surfaces of cells throughout the body, telling the immune system that these cells are friends, not foe.
Cancer cells can take advantage of the same immune checkpoint mechanism, allowing them to escape detection by the immune system. This is where P comes in. P binds to PD-1 on T cells (a type of white blood cell), blocking (inhibiting) the immune checkpoint mechanism, and voila, suddenly the cancer cells are fair game. Unfortunately, this also means that the immune system can now attack normal healthy cells in the body too. The drug is therefore not without its risks, although serious side effects are rare. The idea, though, is that the T cells will go after cancer cells before healthy cells. Why would this be? This is where those mismatch repair (MMR) proteins I mentioned earlier come in; Dad’s cancer is deficient in MMR proteins (dMMR), meaning that the DNA is unable to be repaired properly when errors creep in (sporadic genetic mutations). Cells that are dMMR tend to undergo a lot of mutations and generate novel proteins that look foreign to the body, thus attracting the attention of the immune system. And with the immune checkpoint inhibited, Dad’s T cells are now free to feast away on the cancer to their heart’s content. So as in Dad’s case, having a type of cancer that is dMMR is favourable to the efficacy of the drug.
How is Dad responding to treatment?
Dad had his first P cocktail last Wednesday, so it’s too early to tell if the drug has been effective. So far he’s feeling pretty good, with some fatigue as the only side effect. After three months, his progress will be checked with a scan to assess the size of the tumours. Please pray that he responds well to treatment.
Hooked up to the good stuff, with a coffee and a custard square to sweeten the deal.
Stepping back in time...
While Dad is having his treatment, he needs to be extra-specially careful not to get sick. With his T cells now a loose cannon, any inflammation in his body could attract unwanted attention and potentially lead to serious side effects. Dad’s body needs to be focused on killing cancer, not warding off the latest flavour-of-the month virus being dished out from Winter’s cauldron. For this reason, it’ll be like 2020/2021-level isolation all over again for Mum and Dad (bar the beer and wine), at least until the worst of winter has passed. We appreciate your understanding and are very grateful for your thoughts and prayers, even if they can’t see you in person at this time. They’d still love to hear from you, be that by phone, text, or if you prefer, you can send them a special message by clicking here.
Until next time!
Praise God, from whom all blessings flow
Praise Him, all creatures here below
Praise him above, ye heavenly host
Praise Father, Son, and Holy Ghost!
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