Knowing the history of cancer research informs current treatment and research

TWO-YEAR-OLD GORDON ISAACS, the first cancer patient treated with a linear accelerator, sits quietly while receiving a dose of radiation therapy for treatment of bilateral retinoblastomas in 1957. After the success of the treatment, doctors expanded the use of radiation therapy for cancer treatment. Photo courtesy of National Cancer Institute

A New England man told us that one day his wife noticed yellow markings on his face; emergency room doctors identified it as jaundice. The man was immediately admitted to the hospital where he was given a CT scan due to increased risk for patients his age — 78.

Before he knew it, the radiologist was beside the man’s bed informing him that the CT scan had identified pancreatic cancer.

His first week in the hospital was the “most chaotic week of his life,” he said. There were so many facts to learn about what was going to be done to him and what choices he could make about treatment. At this point, he was faced with three treatment options: surgery, chemotherapy, or a newer option known as immunotherapy.

He felt fortunate to have had his cancer detected in its early stage.

The options this man was offered reflect the current state of the art for cancer treatment, and were built on a history of treatments that have changed over time — and continue to advance.

Treatment of cancer through surgery can range from removing small tumors to entire organs depending on the spread of the cancer. Chemotherapy, introduced by Dr. Sidney Farber’s research in the middle of the last century, treats patients with drugs. Radiotherapy (x-rays) can target cancer cells without cutting open the patient or injecting medicine. Finally, immunotherapy and other newer treatment options are changing the reality for cancer patients in a variety of ways.


Early cancer surgery was championed by William Stewart Halsted, who developed the radical mastectomy in 1894. This surgical practice involved the removal of more and more of women’s chests, hoping the excavation of tissue would eliminate the chance of cancer recurrence.

The practice of radical surgery, popularly used on cases of breast cancer, quickly became a prominent method of cancer treatment as many doctors believed it to be most effective in curing the disease. However, cancer patients, disproportionately women, were being mutilated, and data regarding remission rates showed radical surgery had no more benefit compared to more conservative operations.

In the 1950s, American surgeon George Crile faced backlash from the medical community when he suggested that radical surgery catered more to the surgeon’s needs rather than the patient’s. However, the limitations of surgery and development of other therapies ultimately pushed doctors away from radical operations.

Chemotherapy is perhaps the most widely available treatment for cancer in the present day. It uses chemical agents that kill cancer cells, and was first conceptualized and discovered in the late 1940s by Sidney Farber (after whom the Dana-Farber Cancer Institute is named). The chemicals tend to be highly toxic, meaning that in addition to causing the death of the cancer cells, chemotherapy can negatively affect healthy cells and tissue.

Over time, the use of chemotherapy has shifted to various cocktails as more chemical compounds are discovered and tested. Currently, a patient will often have various options as to the treatment they undergo, depending on the cancer and their condition. Multiple agents are typically given at once, over a period of several months.

While chemotherapy is effective for various, localized and widespread cancers, radiation treatment is particularly effective on localized tumors. Radiotherapy uses very powerful radiation (in the form of X-rays) that is focused on a single point: the tumor. This treatment is mostly used for solid tumors since these are situated in one place, allowing precise targeting. The radiation kills the cancer cells in the tumor, and is often combined with chemotherapy to eliminate the cancer completely.


In the case of the anonymous community member we interviewed, surgery was the best option for many reasons. He was lucky enough to have detected the cancer so early that doctors could remove the tumors with a “Whipple Surgery.” This surgery is far from a radical surgery and only involves cutting away the portions of the pancreas where tumors have been detected. Two months after his surgery, doctors prescribed four months of chemotherapy to ensure the eradication of the cancer.

The man’s treatments involved weekly visits to the hospital, which were eventually downgraded to biweekly visits. We will return to his story after we explain newer treatments for cancer that have emerged.

One example of these newer treatments is immunotherapy. Immunotherapy is an emerging field of cancer treatment that alters the activity of the immune system, therefore slowing or stopping the progression of disease.

In addition to immunotherapy, several other new treatments are being searched for and researched, in the hopes that they can further the progress of the battle against cancer.

The benefits of exercise

An example of a newer indirect treatment of cancer is exercise, which can play a role in reducing tumor growth. Recent studies have shown that breast-cancer-bearing mice that are assigned regular exercise had a 24% increase in survival rate compared to a sedentary control group (Hagar et al., 2019). While future research into this correlation is certainly needed, we might see a rise in prescription of exercise for cancer patients who are capable. It might also be wise for family members at risk of certain forms of cancer to maintain regular exercise in order to increase their chances of survival if they do get cancer, according to the CDC.

Hypoxia-activated prodrugs

Prominent recent work in immunotherapy has targeted the hypoxic environment of cancerous tumors. Hypoxia is the lack of oxygen in the body, which inhibits the productivity of the immune system. Currently, a class of drugs called hypoxia-activated prodrugs (HAPs) is in development and not yet in clinical use. These prodrugs — drugs activated by and inside the body — are triggered under low oxygen conditions. They cause DNA strand breaks and cross-links, consequently killing hypoxic cells.

HAPs are being tested in combination with standard chemotherapy because studies have shown the prodrugs to be ineffective in stopping disease progression when used alone. Chemotherapy is normally inhibited by hypoxia, but is effective when HAPs kill hypoxic cells and normalize the tumoral environment.

Naturally occurring chemotherapeutic agents

Naturally occurring molecules have a long history in cancer treatment and continue to inspire anti-cancer drug development. An East African insect is known to produce a toxin that has anti-cancer properties. The toxin, pederin, has been found in several other organisms, and shows potential in the further development of new cancer treatments. Scientists have found that pederin (and various similar toxins) are produced by bacteria. Researchers have proposed cultivating this bacteria to enable mass production of this chemical, which would increase access to this form of treatment.

Looking at the developments cancer treatment has undergone in the last few decades, it is evident that significant progress has been made, and continues to be made. Nonetheless, as has always been the case, the war against cancer is far from won. With a greater pursuit of treatments, therapies, preventative healthy lifestyles, and a greater understanding of cancer, more people can be spared the ravages of the disease.

Now the results we have been waiting for: What did the next five years look like for the patient that we interviewed?

They were completely normal with no recurrence of the cancer. Considering that there is only a 5% chance of surviving five years after pancreatic cancer, the New England man considers it a miracle that he is still alive.

According to his surgeon, the major contributor to his survival looking back on the experience is likely how early the cancer was detected. The fact that this patient visited the doctor the instant that he showed signs of jaundice might have saved his life.

Learn More About Cancer Treatment

• “The Emperor of All Maladies” by Siddhartha Mukherjee for an in-depth look at the history of cancer treatment

• for further reading on the future of cancer treatments

• to learn more about hypoxia and prodrugs


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