How do chemo drugs work?

I've been doing some research into the drugs I'm having administered in the hospital, and how they're each working to attack the cancer cells in my body. Having chemotherapy is a bit like finding some weeds under a beautiful rose bush, and deciding to spray hardcore weedkiller on the entire garden, just in case the seeds from these weeds have blown anywhere else. In other words, it's not always hugely targeted, but it can be very effective. Cancer cells (as with many other healthy cells) grow by going through what is called the cell cycle, in which a cell divides into two identical cells with their own set of DNA. Chemotherapy drugs interfere with various parts of this cycle so that the cells can't divide or repair themselves if damaged. Normal, non-cancerous cells have a better ability to repair themselves. There are over 20 different combinations of chemo drugs and the exact combo is down to the type of cancer you have, the most up to date research available and the experience and opinion of your oncology team. My cancer is ER+ (Oestrogen receptor positive), HER2+ (Human Epidermal Growth Factor Receptor 2 positive) and Progesterone + so I've been given the following regime of drugs.

The first four cycles I had were called AC, or Doxorubicin (A) and Cyclophosphomide (C). These are both first generation chemotherapy drugs, which mean they've been used for many years and are fairly standard. Doxorubicin (aka 'the red devil') is the red one I was given by hand in the syringe, and it's a type of chemo drug called an anthracycline. It slows or stops the growth of cancer cells by blocking an enzyme which they need to divide and grow. Cyclophosphomide belongs to a group of drugs called alkylating agents. It works by sticking to one of the cancer's DNA strands, which controls everything the cancer cell does. The cell cannot then divide into two new cells.

As we have seen, my 4 x AC cycles have been pretty effective, although I'm glad to see the back of the side effects on those drugs!

My next four cycles are TPH, or Taxotere (the brand name for Docetaxel), Pertuzumab (also called Perjeta) and Herceptin (the brand name for Trastuzumab). I've already had one cycle of this combo and will have three more. All of these are administered via a drip into the hand. The only one of these which is an actual chemotherapy drug is Docetaxel, which is nicknamed 'tax'. It's a third generation chemo drug, which means it's more effective than the first generation of chemo drugs, but brings with it an increased risk of infection. Docetaxel works by disrupting the microtubular network in cells, which is essential for cell division and other normal cellular functions. Docetaxel interferes with the function of microtubules, resulting in inactive microtubule bundles, causing cells to die.

Herceptin and Pertuzumab are actually not chemo drugs, they are monoclonal antibodies, but they are administered with chemo drugs because trials have shown that the effectiveness of both chemo drugs and monoclonal antibodies is dramatically increased if they are given together. Pertuzumab is a relatively recent drug to be licenced for use (December 2016) and at the moment it's only available if you have neo-adjuvant chemotherapy (ie chemo before rather than after surgery). Herceptin is also a relatively new drug and apparently there's a 2008 film called Living Proof starring Harry Connick Jr about Dr. Slamon's discovery of Herceptin. (Fun fact!) I will continue to receive Herceptin for a year through injections every 3 weeks, as well as these four cycles intravenously.

Both of these drugs are immune targeted therapies, which work by targeting specific proteins (receptors) on the surface of cells. Some cancers have too much of the protein HER2 on the surface of their cells (hence are HER2+). The extra HER2 receptors stimulate the cancer cells to divide and grow. Pertuzumab and Herceptin work by locking onto HER2 proteins. Each drug locks on to a different part of the protein. This blocks the receptors and stops the cells dividing and growing.

Here's a handy drawing from a book I have which shows how Herceptin works.

Also, here is a great animated video which really simply and clearly explains how monoclonal antibodies work.

It's incredible what advances in medical technology are being made every day, and I also know women who are taking part in medical trials for even more new drugs, each one potentially more effective than the last.

So I'm currently recouperating from the first TPH cycle which I had last week, and although there are lots of nasty side-effects from the AC which I'm thankfully not experiencing any more, instead they have been replaced by new ones! So no more nausea, constipation or fog-headedness, but hello bone pain, nosebleeds and chronic indigestion. I'm also having terrible sleepless nights which is not aiding my ability to heal. I'm feeling as though I'm operating on the final fumes of petrol in the tank, and I'm not sure where I will get the energy from for the last three rounds.

My neutrophils were incredibly low when I had my bloods done last Monday (they were 0.9 and they won't administer chemo unless they are at 1). Luckily they took my bloods again on the morning of chemo and they'd made it to the required level, but if you see this graph of my neutrophil counts that Tanai drew...

... if they carry on along this trajectory, it's looking unlikely that they will be at the required level by my next scheduled chemo, number 6. It's interesting to see how much they have reduced by each time. I'm trying to think if there's anything I did differently between rounds 4 and 5 which ensured they only reduced by 0.5, but all I can think of is our wonderful restorative weekend at Paddy and Lorraine's. Perhaps the extra relaxation helped! It certainly raised our spirits, so thanks for having us over.

Anyway, I know this post was rather dry and technical but if you got this far, well done for sticking with it, and I hope it was informative!