Identify the enemy, target, and attack—this is the method used in the fight against cancer in the 21st century. By identifying specific targets on the cancer cells and discovering drugs that work on those targets, cancer treatment has now advanced from a “one size fits all” approach to a more personalized one.

For several decades, chemotherapy had been the mainstay of cancer treatment. The discovery of drugs used to kill cancer cells was incidental during World War II. Two scientists, Louis Goodman, and Alfred Gilman, were sent to study the effects of chemicals used in warfare. Thousands were killed by exposure to Mustard gas used in the combat. Gilman and Goodman found that the bone marrow of those who died from exposure to the Mustard gas was devoid of lymphoid and myeloid cells. They used this observation to study the effect of Nitrogen Mustard, a related compound, in eliminating cancer cells from experimental animals. The encouraging results from their study led to human experiments, thus marking the beginning of an amazing journey in the fight against cancer.

Cancer cells, in general, multiply rapidly when compared to normal cells. Chemotherapy drugs kill cancer cells by halting their growth, inhibiting the cell division at different levels. The main disadvantage to this approach is that these drugs are unable to distinguish normal cells from cancer cells. While the growth of cancer cells is slowed down, so is the growth of other rapidly dividing cells. This leads to a lot of unwanted symptoms. For decades, cancer patients, while benefiting from chemotherapy, had to pay a price due to side effects.

Research has been ongoing in minimizing the side effects of chemotherapy as well as finding drugs that focus on cancer cells alone.  Medicines were discovered to focus on individual cancer cells, while minimizing the effects on normal cells. Many types of cancers are now reaching a “cure,” thanks to the successful research on Targeted agents. The perfect example is a type of leukemia called CML (chronic myeloid leukemia). A translocation between two chromosomes and a resultant abnormal chromosome called Philadelphia chromosome is the initial step in CML. The fusion protein (bcr-abl tyrosine kinase) causes abnormal growth of white blood cells and leads to the development of leukemia.

Identifying the target, the Philadelphia chromosome, and the fusion protein, bcr-abl, was a breakthrough in cancer research. For years, a bone marrow transplant was the only hope for cure for patients with CML. Bone marrow transplant is not an option for most patients and carries significant risk. Discovery of a drug called Imatinib (Gleevec) that attacks the fusion protein and thus eliminates the genetic change behind the development of CML opened the road to cure. Now more than 95% of CML patients have benefited from this drug and have been long-term survivors. This marks the beginning of another milestone in the fight against cancer, namely “targeted therapy.”

Another example of targeted therapy is a drug called Herceptin (Trastuzumab) used in the treatment of breast cancer. About 30% of breast cancer patients express a protein called Her-2 on the surface of cancer cells. This sub-type of breast cancer patients historically did worse.  Trastuzumab attacks the Her-2 protein and thus results in improved clinical outcome for Her-2 positive breast cancer patients.

There are newer medicines now, targeting the Her-2 receptor on breast cancer cells.   One such drug is Trastuzumab Deruxtecan (Enhertu). Studies have shown that patients getting Enhertu had significant improvement even in advanced breast cancer.

Hundreds of new targeted agents are now being used in various cancers, either alone or in combination with chemotherapy. Many more drugs are in the pipeline and are being studied extensively.

Targeted agents are also used in different types of lung cancer, based on mutations and other molecular changes on the cancer cells.

Now cancer cells are also analyzed in detail, to identify the factors that predict the risk of relapse and response to a specific treatment. What works for one person may not be beneficial for another. Cancer cells are unique, just like individual patients, and cancer treatment is also tailored accordingly.

The advent of targeted therapy signals a bright future for millions of cancer patients and their families.

MBBS, MD, FACP - Medical Director & Consultant Oncologist, Oncology Centre at Dr. KM Cherian Institute of Medical Sciences