A Brief History of Cancer Treatment—Where Chemotherapy Began, How it Evolved, and What’s Next

The history of chemotherapy goes back a little further than the early 20th century. In 1890, German scientists and eventual Nobel Prize winners introduced the first serum therapy that proved immunity could be transferred. With this discovery, chemotherapy and immunotherapy was born.

Early Chemotherapy

The first decades of chemotherapy research were weighted towards the development of models that reliably represented cancer in humans. Leo Loeb and Carl Jensen successfully transplanted tumors in rodents. This facilitated the testing of a large number of drugs on living animals, although the work was hampered by the lack of suitable clinical facilities.

This early work achieved little more than to establish a poor reputation for the use of chemicals to treat cancer. Despite the U.S. Office of Cancer Investigations testing more than 3,000 compounds between 1935 and 1953, only two drugs advanced to clinical trials. These compounds then proved to be so toxic that the research was dropped completely.

Advancements in World War II

The next step breakthrough in chemotherapy was an indirect consequence of World War II. Advancements in chemotherapy were an unexpected byproduct of research into battlefield gases and the treatment of battlefield wounds.

The accidental spillage of mustard gas in Bari Harbor, Italy, sparked the first discovery. Doctors noticed that sailors exposed to the gas suffered bone marrow depletion and lymph node suppression. This led to the granting of a license to study the potential benefits of mustard gas for the treatment of cancer. The results of this research showed a marked regression in lymphoid tumors in mice. Although wartime secrecy meant the results were not published until 1946, the discovery eventually led to the oral derivatives of alkylating compounds like cyclophosphamide, used to treat leukemia and lymphomas.

Secret war research into creating antibiotics to treat battlefield wounds found some of these antibiotics had antitumor effects. This led to the development of actinomycin D, which went on to be used in the 1950s and 60s to treat certain pediatric tumors.

From Poison to Cure

This initial optimism for chemotherapy in the late 1940s was short-lived. It rapidly became apparent that remission did not last long, so the dismissive attitude over the potential of chemotherapy reemerged. Scientists who chose to pursue this field of research were often treated with disdain by their colleagues and some were even threatened with dismissal from their laboratory.

Undeterred, some scientists continued to pursue their vision of using chemicals to kill cancer. In the mid-1950s, Charles Heidelberger and his colleagues at the University of Wisconsin recognized the liver preferentially absorbed uracil, which allowed him to develop a targeted form of the drug by adding a fluorine molecule. This drug marked the beginning of targeted chemotherapy.

Around the same time, the interest in treating childhood leukemia was growing. A number of research establishments combined their skills to review existing knowledge, which established the foundation for modern research standards of statistical analysis, protocol development, and clinical trial design.

Through the 1960s, chemotherapy was still regarded as an underclass of treatment, and the drugs were often referred to as “poisons.” The discovery of procarbazine, a treatment for Hodgkin’s disease, completely shifted attitudes.

With the introduction of a combination chemotherapy using a variety of drugs including procarbazine, the remission rate went from zero to 80%. Building on this work, treatments for acute leukemia, lymphoma, and breast cancer were developed through the 1970s.

“The War on Cancer” picked up through the 70s and 80s with the evolution of targeted chemotherapy agents. The sophisticated molecules which exactly fit unique sites on the cancer cell and inhibit its function. The first effective targeted agent succeeded because the cancer was caused by a single mutation, so the race was on to target cancers caused by multiple mutations.

Chemotherapy Today and Tomorrow

The millennium saw major strides in chemotherapy with advances in genome sequencing that opens the door to the development of targeted drugs. A new generation of protein kinases fights solid tumors by interfering with the workings of the cancer cell while leaving normal tissue untouched.  In addition, the exploration of the potential immunotherapy offers great hope for ‘living drugs’ where T-cells are programmed to seek out and destroy cancer cells. This treatment also offers the promise of life long cancer protection as the T-cells pass on their ‘memory’ down successive generations.

Chemotherapy started as an imperfect treatment and, in many ways, it still is. But the science of cancer treatment has come a long way from “poisons” and mustard gas

 

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