In less than one-year, scientists created not one, not two, but three vaccines with over 90% efficacy for Covid-19. Which begs the question, what gives? Why don't we have cures for all our other ailments? After spending billions of dollars on cancer research for decades, where is that cure? Regrettably, there is none. And it's not in a vault protected by the government and big pharma either. The reality is, cancer is extremely hard to treat, study, and understand.
Infectious disease vs. cancer
Infectious diseases are easily targeted in comparison to cancer cells. Bacteria have a unique cell wall compared to animal cells. Some antibacterial medications attack their membranes and cell wall synthesis, killing bacteria and minimally harming ourselves. Bacterial enzymes differ from animal enzymes, too. Newer antibacterials inhibit bacterial proteins, leaving our enzymes unperturbed. Viruses are also easily distinguished from our cells. They produce their own distinct proteins and have unique genes. We use vaccines to train our immune system to be alerted to their "foreign" presence.
But cancer cells? They're a bit trickier than bacteria and viruses.
What is cancer?
Cancer is a mass of our cells that have uncontrolled growth, avoidance of cell death, and the annoying habit of acquiring genetic mutations that enable unwanted behavioral adaptations. Ironically, killing a cancer cell is easy; we do it in test tubes all the time. The challenge is killing the cancer cells and not our healthy cells. Unlike bacteria and viruses, cancer cells have our genes, our proteins, and our molecular machinery. So how do we kill cancer cells inside a human body?
The answer lies in the research. Through years and years of experimental research, we are learning what makes cancer cells tick. By figuring out how cancer cells behave differently, anti-cancer drugs can be designed that do not harm non-cancer cells.
What makes a cancer cell?
It all comes down to abnormalities in the DNA. Genetic mutations can be inherited from your parents, acquired over time due to general wear and tear, or result from environmental stress (cigarette smoke, UV, etc..).
We have an increased susceptibility to cancer when an oncogene or tumor suppressor is mutated. Oncogenes are genes that contribute to cancer if they are over-expressed or hyper-activated, i.e., epidermal growth factor receptor (EGFR). Tumor suppressors are genes that, if turned off, contribute to tumorigenesis. The most famous tumor suppressor is P53, a protein that signals cells to die. When P53 is weakened or inactivated, cells don't die when they are injured or malfunction.
Having one mutation in an oncogene or a tumor suppressor may increase the probability of getting cancer, but it won't cause cancer on its own. An estimated 2-6 cancer-related genes must be mutated for tumorigenesis, and further mutations can contribute to disease severity.
Barriers to treating cancer.
Cancer is a heterogeneous disease. When we refer to cancer, we are not mentioning one disease, but a family of hundreds of diseases. A treatment that works well for breast cancer might not necessarily work for pancreatic. To complicate matters further, each tumor can be characterized by its unique genotype, meaning that not every patient will respond to treatment similarly.
Cancer cells mutate and adapt. After wrapping your head around the infinite permutations of cancer types and genotypes, also consider that an individual tumor may be heterogeneous as well. Cancer cells divide so quickly in stressful environments that they often incorporate mutations during DNA replication. Mutagenesis creates subpopulations within a tumor, causing issues such as metastasis and chemotherapy resistance.
The difference is subtle. As mentioned, the drug designed to kill cancer cells shouldn't poison the rest of our body. But if the difference between the cancer cells and our cells are only 2-6 genetic mutations, designing a specific drug is no trivial task. Currently, most chemotherapies are designed with one of the following anti-cancer strategies:
Modeling Cancer. Early cancer research takes place in test tubes. Protein function and structure are investigated in solution, while cancer cells are manipulated in dishes. When in vitro studies seem promising, experimentation moves on to mouse models. Unfortunately, what works well in a test tube often does not work well in the body. And sometimes, a drug that works marvelously in a mouse is toxic to humans. Therefore, preclinical studies are tweaked and repeated extensively to ensure that clinical studies are as safe as possible. Computational models can help bridge the gap between animal testing and human testing, but with limitations. On average, it takes 30 years from drug design to clinical trial approval. And as careful as scientists are during those 30 years, cancer clinical trials have the highest failure rate. Most trials fail due to adverse side effects (aka: when the drug also attacks our healthy cells).
So, will there ever be a cure?
To answer that question, we'd have to define the word "cure." A cure is a gold-standard treatment to eradicate or alleviate a disease completely. To date, only two diseases have been successfully eradicated from the earth, smallpox and rinderpest (both viruses that were wiped out by vaccination — yay, vaccines!).
Likely an end-all cure to cancer is not in our near future. But wait! Before you close out of this blog post, annoyed by my pessimism, I have a message of hope for you. Although "cures" are not on our immediate horizon, adequate treatment and prevention are already here — with more to come. Let's look at breast cancer as an example. In 1971 the 5-year survival rate of all breast cancers was 53%. Today, the 5-year survival rate is nearing 90%! Encouraging numbers, to say the least, these stats are representative of the advancements made in cancer research.
Cancer researchers have chosen an arduous career, often riddled with disappointment and setbacks. Although earth-shattering, groundbreaking discoveries are preferred, in science, it's often the small victories that will culminate in clinically relevant treatments. Cancer research may seem slow, but it is undoubtedly progressing.