Only a few months back, during the height of the Omicron wave, the American Cancer Society released its annual report, which detailed a dramatic 30% decrease in cancer-related mortality, over the past two decades. This finding is attributed to improvements made to early detection tools, as well as to the development of innovative cancer treatments.
Despite the fact that, historically, “cancer” has essentially served as a synonym for a horrible, incurable disease, a breath of fresh, optimistic air has been circulating through the oncology community in recent years. Modestly and with determination, without those grandiose moments experienced upon the discovery of penicillin or the development of the polio vaccine, the scientific community has spent recent decades slowly advancing, heel to toe, towards the healing of many forms of cancer, transforming the most threatening diagnosis of all into a chronic illness.
Humanity’s battle against cancer began to bear fruit over the course of recent decades. That said, these fruits are the products of hundreds of years of continuous effort during which, there have been both brilliant victories and jarring failures. The more we learned about cancer, the more we discovered how little we actually understood the disease. The more we developed innovative medical treatments, the more we revealed just how complex cancer really is, and just how badly it can throw us for a loop. Nevertheless, we currently find ourselves at the dawn of a new era in cancer treatment; the past 10 years have brought unprecedented scientific and technological advancements and, for the first time, we are seeing later-stage cancer patients recover from the disease, thanks to advanced diagnostic tools and medications.
Over the course of the history of medicine, five major revolutions can be identified as having pivotal roles in bringing us to where we are today, closer than ever to beating cancer:
The surgeon’s knife
Cancer is perceived to be a modern illness – the new era’s plague – but it has been around since the dawn of time, and has plagued humankind ever since. The first documented cases of cancer appear on ancient Egyptian papyruses, dated back to over 4,000 years ago. The Egyptians viewed cancer – a mysterious disease characterized by the appearance of foreign masses in patients’ bodies – as the expression of an aggressive desire, and had very little motivation to treat these patients. The very few attempts to remove the masses were disastrous. It took many years for surgery to become a medical discipline.
In ancient Greece and later on in Europe during the Middle Ages, operating on a human body was considered taboo and forbidden, for religious reasons. As a result, a deeper understanding of human anatomy only appeared in the 15th and 16th centuries, when veneration of the church began to decline in Europe. Slowly but surely, surgery became an accepted medical practice. The surgeon’s knife became a magic wand of sorts; one that could be used to resolve infinite medical states that were, until then, deemed hopelessly incurable. Cancer became surgeons’ prime target. If cancer was a foreign body within the patient’s body, then all that needed to be done to cure the disease was to simply remove it.
At the end of the 19th century, oncological surgery became an official specialization, and cancer surgeons were awarded “demi-god” status. The more that surgery advanced as a field, the more power surgeons had to cope with more and more types of cancer. The famous radical mastectomy, developed by Dr. Halstead to remove breast tumors, has led to high patient healing rates and was the standard of care until the 1970s. That said, the limitations of surgery quickly revealed themselves; among most patients, the operation only helped for a limited amount of time, before the tumor resumed its attack, usually with a vengeance. Just like the mythical Sisyphus, surgeons removed the tumors over and over again, waging an unwinnable (and pointless) battle. It took time for surgeons to understand where they went wrong; when tumors were discovered at an early stage and limited to the source organ, surgery was extremely effective and led to healing. However, in most cases, by the time patients went under the knife, the tumor was already at a more advanced stage, having sent rogue and undetected cells to other parts of the body. In such a case, surgery would be nothing more than an attempt to bandage a bleeding gunshot wound – too little, too late. To date, the surgeon’s knife is an extremely effective tool in early-stage cancer treatment, but to overcome more advanced diagnoses, innovative tools capable of waging war against any microscopic cancer cells left behind after the surgery is necessary as well.
We’ve all encountered invisible X-rays at one point or another in our lives. Discovered by German physicist Wilhelm Rontgen, X-rays, a tool that exposes various bodily organs to radiation, significantly changed the world of medicine. Rontgen broke through the sensory limitation to penetrate and examine the body, without opening it up. The X-ray’s ability to be immediately used for medical purposes was, of course, leveraged for diagnostics: to identify fractures, diagnose pneumonia, or plan a surgery to remove foreign objects from the body. X-ray machines rapidly became a most basic and essential diagnostic tool, much like stethoscopes, thermometers, and blood tests.
Less than a year following Rontgen’s discovery, it was determined that X-rays were not just a breakthrough diagnostic tool, but rather, they could also be used as a revolutionary tool to treat cancer. Doctors who used X-ray machines on a daily basis to render diagnoses discovered that burns appeared on body parts that were exposed to radiation. They understood that the X-rays penetrate the body’s tissues, enabling them to view the body from the inside, while also leaving a mark on the cells the X-rays pass through. This was a scary discovery, but one the doctors viewed to be full of potential; any substance capable of destroying healthy tissue can also be used to destroy sick tissue. This is how Rontgen’s discovery led to the development of radiotherapy: the treatment of cancer using X-rays.
Using radiation to treat tumors was determined to be effective. At the start of the 20th century, it became a complementary treatment, used in conjunction with surgery. While the surgeon’s knife was responsible for removing the tumor itself, the X-ray’s invisible “knife” began to be used to destroy the rogue cells surgeons left behind. Unfortunately, this course of treatment was also revealed to have limitations. The vast damage that it causes to bodily cells prevents X-rays from being used across the entire body. Surgery and radiation improved doctors’ abilities to treat early-stage cancer patients, but the more advanced cases were still left without an effective course of treatment.
The poison that became a healing drug
Like the best scientific discoveries, chemotherapy was discovered serendipitously. After chemical weapons were used during the first World War, researchers discovered an intriguing phenomenon among soldiers who were exposed to the deadly weapon: their white blood cells were all but eviscerated from their bodies. This was a fatal blow for the soldiers, but it unearthed a very interesting property of the poisonous mustard gas – its ability to quickly kill dividing cells, such as white blood cells. If cancer is characterized by the rapid division of cells, a substance such as mustard gas could serve as the ultimate cancer treatment.
In the 1940s, the development of mustard gas derivatives and other chemical materials led to the birth of chemotherapy. The first patients to benefit from this treatment were children with leukemia. Those who were, until then, sentenced to certain death, were healed within a few short weeks of undergoing chemotherapy. The same substance that destroyed soldiers’ white blood cells while they were at war also destroyed the uncontrollably dividing white blood cells of very sick children. To date, this is one of the greatest medical achievements in history. Thanks to chemotherapy, children suffering from acute leukemia now have a 90% survival rate. Humanity succeeded in quickly transforming a weapon of mass destruction into a lifesaving drug.
However, physicians struggled to replicate this success when treating other types of cancer. Chemotherapy may have improved and lengthened the lives of many patients, but stories of chemo providing a cure like it did for those children are all but nonexistent. There are many issues with chemotherapy, with its high levels of toxicity topping the charts. Chemotherapy is not specific to cancer cells either. This rapid cell division does characterize cancer cells, it also characterizes quite a few healthy cells. Chemotherapy’s inability to precisely differentiate between healthy and cancerous cells renders it a limited tool; chemo kills hair follicles, intestinal lining cells, and immune cells. The dose required to eradicate a tumor can, sometimes, kill the patient before it kills the growth. To beat cancer and deal it a precise blow, its root must first be understood. As years went by, scientists discovered that the rapid division of cancer cells is the result of the cancer, rather than its cause. The reason for the cancer’s appearance was rooted in the patient’s DNA.
Hitting the target
In 1953, Watson and Crick, two British scientists, discovered the structure of DNA and drastically altered our understanding of life on earth. DNA is a chemical code with three billion “letters” that is found inside each and every one of our body’s cells. It serves as a sort of instruction manual on how our body is to produce proteins, its main building blocks. For the most part, genetics dictates who we are, from the color of our eyes to our IQ, to our tendency towards feeling happy or sad. One way or another, every fiber of our being is affected by the DNA in our bodies.
Above all, genetics plays a pivotal role in our health. Tiny changes to our genetic code can influence our body’s ability to function, and they can bring on various illnesses and diseases. In the second half of the 20th century, genetics research began to accelerate, thanks to an increased ability to “read” genetic code, leading to medical breakthroughs, including in cancer research. If, until then, cancer was perceived as a disease that was caused by an external instigator, such as a virus or pollution, the 1970s brought with it the discovery that most cases of cancer are integral to, caused by an amalgamation of genetic mutations that take place sporadically our lifespan, inhibiting the cell’s ability to properly divide.
This revolutionary discovery led to a change in the cancer treatment paradigm. There was no longer a need to attack cancer with chemicals that killed every diving cell without discernment. Rather, only those specific mutations that led to the uncontrollable proliferation of cells should be targeted. And so, a new generation of treatments called “targeted therapies” made their way into the world in the 1990s. These treatments were directed at those – and only those – cancerous mutations. Hundreds of different genes have since been proven to be involved in cancer, and tens of new drugs were developed to cope with these changes. These drugs were found to be extremely safe, as they almost never harmed healthy cells. What’s more, they transported the field of oncology into an era of “personalized medicine.” Since each targeted therapy acts upon a certain gene, there’s no point in giving it to every patient, but rather it is only administered to those who carry a mutation of the same gene. Chemotherapy’s approach, according to which everyone receives the same course of treatment, was rendered obsolete. A breast cancer patient and a patient suffering from lung cancer can carry the same gene mutation and, therefore, require the same treatment, while two breast cancer patients may need drastically different treatments.
The transition from anatomical medicine, which places the patient’s organ front and center, to molecular medicine, which places the patient’s affected gene center stage, brought with it effective targeted therapies. Nevertheless, targeted therapies have also been unable to secure successful outcomes for most cancer cases. Tumors are not created from a single mutation, but rather from a network of tens of mutations that work together to enable cancer to flourish in the patient’s body. A drug’s attack against a single cancerous gene will lead to the activation of a second cancerous gene, attacking the second gene will lead to the activation of a third, and so on. Cancer cells are complex machines that frequently evolve and undergo genetic changes that enable them to develop a resistance to most targeted therapies.
The cancer disguise
The fifth – and potentially the largest – revolution is that of immunotherapy, which first appeared in the previous decade. Besides the genetic changes that are required in order to transform a healthy cell into a cancer cell, there’s another important characteristic that enables cancer cells to develop in the human body; their ability to evade the immune system. The immune system is a smart system that has, over the course of millions of years, refined its ability to identify foreign cells in fected with viruses or mutations, and destroy them – quickly and efficiently. Cancerous mutations can develop in a healthy person’s cells as well, but those are immediately eviscerated by their immune system. That said, cancer cells are able to masquerade as normal cells, and make a mockery of the immune system. These cancer cells camouflage themselves by affixing a protein to their backs. This protein links to the immune system and signals that the cell is normal and does not need special attention. In this way, the cancer can continue to develop without interruption.
The discovery of this evasive mechanism led to the development of new drugs designed to expose the tumor’s existence to the immune system, thereby enabling it to do its job. These drugs have since been proven to perform exceptionally. For the first time since children with leukemia were healed by chemotherapy, the oncological community began to chatter about a cure. Only this time, the cure is referring to later stage cancer diagnoses that were, up until recently, thought to be incurable – the greatest challenge of treating cancer to date. And so, patients with advanced skin and lung cancer who, up until 10 years ago would have been left with just months to live, are now able to extend their lifespans by years, and even make complete recoveries, thanks to immunotherapy.
In essence, the dramatic decrease in cancer-related mortality mentioned at the start of this article, is, in large part, due to the breakthrough that is immunotherapy. The report claims that the lion’s share of the improved cancer survival rates began in 2015, when immunotherapy was first approved for use by the FDA. Like all the other revolutions mentioned above, immunotherapy is far from putting an end to the battle between humanity and cancer. Many cancer patients do not respond to immunotherapy, and scientists have yet to understand why one patient responds to treatment, while others do not. That said, 2022 is a new year. In 2022, we hope that the Covid-19 pandemic will be eradicated, and that we are on our way to ending cancer’s perilous reign as well, whether via new early detection methods that identify tens of types of cancer with a simple blood test, the use of artificial intelligence to better plan molecules and clinical trials, or smarter immune system engineering. We are at the height of cancer treatment innovation and we cannot be stopped in our tracks. It might take a decade… or two, or three… but, at the end of the day, humanity will exit the war on cancer with the upper hand.