Our evolving war on cancer
The oldest known description of cancer appears in an ancient Egyptian textbook, dating back to 3,000 BC. The papyrus describes several maladies and their cures, but for cancer it simply states, “no treatment”.
For thousands of years we have pitted ourselves against the beast that is cancer. But like the monster from Greek mythology, the hydra, cancer is a many-headed serpent, making it a formidable enemy. Facing the creature, we may try to defeat the beast by drawing your sword and cutting off its heads. This is the image that might have captivated the imagination of early doctors treating cancer.
Under the knife
For a long time, performing surgery and cutting out the tumour was the only treatment option available to people with cancer. The advent of anaesthesia in 1846 made this process a lot more bearable, for both the surgeon and the patient. It allowed surgical pioneers like William Halsted to flourish. Halsted’s surgical techniques, developed at a time of little to no understanding of cancer biology, were brutal. He pioneered the radical mastectomy, a breast cancer surgery that removed not only the entire breast, but the surrounding tissues, sometimes as deep as the chest wall. This would leave patients scarred and often disabled for the rest of their lives. In Halsted’s time, removing every scrap of cancer with the knife seemed like the only way to cure someone. Nearly a century later, clinical trials would show that this radical form of surgery was in no way superior to a more minimal removal of breast tumours.
Surgery only works if you can guarantee that every cancer cell has been taken away. If not, the cancer can come back. The hydra regrows its heads. And if the cancer has spread to other parts of the body, then surgery is fruitless. No amount of cutting will kill the beast.
In 1896, a new kind of weapon was discovered: the mysterious X-ray. Within months of Wilhelm Roentgen’s discovery, X-rays were being used to diagnose cancer, and within 3 years they were used as a treatment - the early stages of radiotherapy. Unfortunately, it took until the early 20th century to discover that radiation could cause, as well as cure cancer. Until then, radiologists often tested radiation strength before treatment by directing the beam at their own skin, waiting for it to turn a nice shade of pink.
Over the decades, radiotherapy has evolved into a highly sophisticated treatment, which can be used before, after and even during surgery. Charring the stump of the decapitated hydra can stop the head growing back. But often not permanently.
As is common in times of despair, humankind turned to warfare. Research into the properties of mustard gas used during the Second World War revealed that its chemical cousin, nitrogen mustard, was surprisingly good at killing cancer cells. In search of other cancer killing chemicals, the legendary cancer researcher, Sidney Farber, discovered that aminopterin, a compound related to the vitamin folic acid, could put children with acute leukaemia into remission. With the first chemical “cure” for cancer, the era of chemotherapy had begun.
The use of chemotherapy alone, and in tandem with surgery and radiation therapy, has become the main treatment regime for different types of cancer - giving back years of life to many patients and curing others. Still the beast could not be defeated. People thought to be “cured” would return to the clinic with aggressive cancers that were no longer affected by the drug that initially killed it. The hydra, wounded with sword, fire and poison, shook off whatever was thrown at it and regrew its heads stronger than ever before.
Targeting cancer’s weak spots
To defeat the hydra, we needed to understand the beast in more detail. With a better understanding of cancer and cell biology, researchers were able to develop treatments that were targeted at certain weak spots of cancers.
One of the first examples of targeted treatment is a drug called tamoxifen. Starting its life as a failed attempt to develop a contraceptive, it was later recognised as a potential treatment for oestrogen-dependent breast cancer. Eight out of 10 breast cancers rely on oestrogen for their growth and tamoxifen targeted this Achille’s heel by blocking oestrogen from interacting with the cancer cells. This targeted treatment turned out to be immensely successful and has saved millions of lives around the world. But tamoxifen’s journey doesn’t seem to be over just yet. Recent research has shown that tamoxifen can also prevent cancer and is now offered to some women at high-risk of breast cancer as a way to reduce their risk.
The introduction of targeted therapies is the first time that we had a chemical weapon against cancer that didn’t also cause massive damage to healthy cells. Chemo- and radio-therapy kill healthy cells, as well as cancer cells, severely limiting the dose and strength we can use to attack cancer. Targeted therapies allow us to target a specific feature of cancer cells, leaving the majority of our healthy cells untouched. Some are designed to inhibit molecular signals that usually stimulate cell growth, but which have gotten out of hand in cancer. Others focus on trying to stop the tumour from building its own blood supply, thereby starving the tumour of nutrients. And others try to trick the cancer cell into committing suicide via a process called apoptosis. These treatments have vastly improved survival for patients, but although we have these powerful new weapons, we still haven’t managed to keep the beast away. For many people, even after an all-out assault, the hydra remains, standing strong.That brings us to the main problem facing cancer researchers today. Cancer adapts, evolves and it grows back. It takes the hit and gets right back up again. The hydra returns to the battle, armoured and resilient to the weapons we used to fight it.
Luckily, we can adapt as well. Research has started to turn its attention to one of the biggest problems in cancer treatment: how do we stop cancer from changing, growing and spreading? Recent research has revealed how cancers do it, but what can we do to stop it? Stay tuned and find out next week in the second part to this blog post.