It's often believed that cancer results from a modern lifestyle, i.e., eating more processed foods, increasing exposure to various radiation sources, and the general fast pace of life. The truth is that the earliest report of cancer, or the disease that later became known as cancer, dates back to around 1600 BC in ancient Egypt. Yes, perhaps the modern lifestyle has increased cancer cases, but it has also provided us with the necessary technology to detect the disease earlier and treat it more effectively. It should also be noted that humans live significantly longer now than a century or two ago, so naturally, the incidence of cancer will increase.
Cancer treatment comprises of three different areas, surgery, radiation, and chemotherapy. However, when you think of a cancer patient, it is the jarring side effects of chemotherapy that come to mind. While there are many resources on the internet to describe the different side effects of chemotherapy and how to deal with them as patients or caregivers, they rarely discuss the mechanisms through which the drugs work.
Cancer arises from a change in the DNA of a single cell that causes it to multiply and grow unchecked. The causes are varied, such as exposure to too much radiation (which is why radiology technicians walk out of the room when taking an X-ray), exposure to chemical carcinogens such as tobacco smoke or asbestos, viruses such as HPV, or copy errors during DNA replication. These events give rise to the same problem: a cell that replicates faster consumes more resources and does not die when it should. And here lies the crux of the problem: cancer cells are not that much different from healthy cells, so anything that kills the cancer cells will likely kill the healthy cells as well. The trick lies in killing the cancer cells faster than the healthy cells.
"Cancer therapy is like beating the dog with a stick to get rid of his fleas."
How to get away with killing cancer
Since cancer cells grow and replicate faster than healthy cells, most anticancer drugs aim to inhibit the replication process. This can be achieved through targeting DNA or proteins related to cell replication, obstructing the metabolism of the cells, or impeding cell division. Some commonly used drugs like oxaliplatin and carboplatin are involved in all three processes and are referred to as cytotoxic compounds.
And now for the kicker: cancer is treated with a combination of the different types of drugs with varying therapeutic mechanisms for specific cancers in different patients. Therefore, each cancer patient receives a cocktail of various medications that have been optimized to treat their particular cancer.
The compound classes that target DNA include alkylating agents, anticancer antibiotics, and some transition metal complexes. These compounds bind directly to the DNA, climbing in between the DNA base pairs or associating with the DNA so that the DNA cannot be replicated. The inability to replicate DNA causes the cancer cell to senesce (stop multiplying) or die.
Interfering with metabolism
Drugs targeting metabolism include antifolates and antimetabolites, which replace compounds in the cell's metabolic cycle. I.e., folic acid is crucial in cell growth and replication, so antifolates take the place of folic acid but do not perform the necessary functions, so the cancer cells are essentially starved.
Blocking cell division
Antimitotic compounds target cell division, and the most used compounds are plant alkaloids such as vincristine and vinblastine. These compounds prevent the formation of microtubules that guide the separation of cells during mitosis. So, if the cells cannot separate, they cannot replicate.
Right on target: creating cancer-cell specific therapies
While the above mentioned compounds are very effective in treating cancer, they do not discriminate between healthy cells and cancer cells, which gives rise to the nasty side effects we have come to associate with cancer treatment. A more recent class of compounds called "targeted therapies" provide more selective interaction with cellular components specific to the cancer cells.
Targeted therapies include:
At the intersection of cytotoxic agents and targeted treatments lies hormone therapies and kinase inhibitors. While they are more selective towards the cancer cells, treatments may still negatively impact the patient.
Hormone therapy can treat hormone-dependent cancers, such as certain types of breast, ovarian and uterine cancers dependent on estrogen and certain types of prostate and testicular cancers dependent on testosterone. By cutting off access to the necessary hormones, the cancer cells are starved of an essential building block. Removing the hormone from the rest of the body also has extensive side effects relating to fertility, secondary sex characteristics, and sexual performance. Still, the side effects are generally less detrimental than other cytotoxic agents.
Kinase inhibitors target kinetic enzymes that contribute to cell growth. Some cancers express more of a particular kinase than healthy cells, while other cancers express a mutated kinase that is specific to the cancer cells. The mutated KRAS has been a holy grail in medicinal chemistry since it is found in numerous high fatality cancers. The development of an inhibitor has long eluded scientists; however, the FDA recently approved a KRAS inhibitor, Lumakras.
And finally, the current buzzword: immunotherapy. Immunotherapy involves using antibodies that bind proteins specific a cancer cell, thereby recruiting the immune system to clear the cancer. Immunotherapy is the most specific chemotherapy available, but since it is so specific, the number of cancers that can be treated are still limited. Personalized treatments come into play here, where a sample of a patient's cancerous tissue is used to develop an antibody for that patient, like designing a key for a specific lock.
Personalized treatments are still highly specialized and expensive pursuits, yet they might become the future of cancer treatment. Immunotherapy also includes the development of cancer vaccines, such as mRNA vaccines targeting KRAS.
For further reading on the topic, I highly recommend the Pulitzer Prize-winning book by Prof. Siddhartha Mukherjee, The Emperor of all Maladies. The book is accessible to scientists and non-scientists alike and does not assume any knowledge in the field of cancer biology. It tells the tale of how theories around cancer evolved and how the current treatments were discovered and refined, all interspersed with gripping tales of the author's own experiences as a practicing oncologist.
Similarly, the National Cancer Institute's website also provides a lot of practical information if you or a loved one is currently busy with cancer treatment and need some guidance.