Chemotherapy: The Good, The Bad and The Future

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Is it true that chemotherapy can give you cancer?

Someone asked me this once, and announced that if they were to ever get cancer, they would reject chemotherapy because they wouldn’t want to “lose their dignity”. When we think about chemotherapy, we think of alopecia (hair loss), nausea, weakness, weight loss, immunodeficiency, among other terrible things. Some patients fear chemotherapy more than the cancer itself. What makes chemo so scary? Why does it have to be this way? I try to answer some of these questions briefly, and comment on targeted therapies as cancer treatments of the future (I’m being quite optimistic here).

According to the website WebMD, chemotherapy is defined as a type of treatment that uses drugs to destroy cancer cells. Simple, right? Not really.

Chemotherapy is one of the most effective ways of treating some cancers. However, the treatment has a dark side because of its effect on healthy cells. When Sidney Farber, the father of modern chemotherapy, used aminopterin to treat childhood leukaemia in 1947, the trial was viewed with equal amounts of enthusiasm and concern.  In the original study, Farber expressed his concerns over non-specific cytotoxicity (cell killing), stating “The toxic effects are stressed in these histories, and the temporary nature of the remission is emphasised.”

But why do chemotherapy based treatments conveniently ignore the fundamental doctrine of medicine, i.e. Primum non nocere (First, do no harm)? This can be explained by introducing what is called the “therapeutic window”. It is defined as “the range of dose which produces a therapeutic effect without causing any significant adverse effects to the patient”. Simply, antibiotics have a wider therapeutic window due to the significant differences between human and bacterial cells, leading to drugs that can target the foreign cell, leaving the host cell unharmed. Cancer cells, however, are so similar to their originators (normal human cells) that designing a drug specific to them has been an exceptionally daunting task.

This means that almost all chemotherapeutic drugs developed initially were non-specific. While the success of conventional chemotherapy lies in producing cytotoxicity, the narrow therapeutic window implies that normal cells would inevitably caught in the crossfire. Simply, the question is: How many cancer cells can we kill, without killing the organism itself?

Most chemotherapeutic drugs inhibit cell proliferation by affecting the synthesis of DNA, or by introducing damage to the genetic material. Since cancer cells divide much rapidly as compared to normal cells, the drugs seem to work by producing DNA copying errors leading to cell death. However, other tissues that contain fast-dividing cells are also affected, including the lining of the gut and hair follicles. This leads to baldness and nausea, some of the side effects most commonly associated with chemotherapy in cancer. There are other side effects involved with chemotherapy, which differ based on the drug used. If you have been advised chemotherapy, kindly ask your Doctor for advice.

Coming to the initial question. Yes, some chemotherapy drugs can, in fact, increase the risk for secondary cancers. Quite ironic, indeed. Due to their method of action involving DNA damage, these drugs can sometimes lead to the development of secondary cancers unrelated to the primary cancer. While chemotherapy induced secondary cancers are usually blood cancers (such as leukaemia), some solid tumors can also result from chemotherapy, such as testicular cancer. This web page by cancer.org briefly deals with chemotherapy and its link with secondary cancers, and is worth looking at.

While I have taken time to write a blog post about the side effects of chemotherapy. I, by no means, intend to discourage anyone from receiving chemotherapy as treatment if advised. Chemotherapy can be an extremely powerful weapon against some form of cancers, and can lead to impressive regressions. Remember to always consult your Doctor regarding potential adverse effects and success rates, when in doubt. Make sure you make the right decision!

The next question is: What are we doing to help change this? With the advent of molecular biology, cancer has been classified and sub-classified based on subtle molecular differences. Some cancers can be addicted to a certain oncogene. Identifying such addictions can reveal a cancer’s weakness (Achilles heel, if you will). For example, CML’s (chronic myeloid leukaemia) addiction to the BCR/ABL protein lead to the development of imatinib, a targeted drug that has proved to be (sort of) a miracle drug for CML patients. Being tailored to target a cancer-specific molecule, targeted therapies widen the therapeutic window for cancer treatments, leading to impressive results.

The hunt is on for other targets, and improved personalised medicine may prove to be the elusive “cure” we’ve always hoped for. More about targeted therapies in the next post!

What comes to your mind when you think of the word ‘chemotherapy’? Do you have any other questions? Leave them in the comments below. 

Further reading:

How Chemotherapy Drugs Work – American Cancer Society

How Chemotherapy Works –  National Institute of Health

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