Written by Ujwal Aluru
One of the hallmarks of cancer is how frequently relapses occur among patients after receiving treatment. Sometimes, this is due to an insufficient amount of therapy, leaving cancer cells behind and allowing them to proliferate. However, it is more likely that these relapses occur because of ineffective treatment rather than an insufficient amount of treatment. Intrinsic or acquired resistance to chemotherapy entail ineffective treatment [2]. So which characteristics cause chemotherapy resistance in cells, and how are those traits spread?
The prevailing idea that “resistance arose from overgrowth of resistant cell clones due to new mutations” was recently proved incorrect [1]. Furthermore, the spread of resistant traits among cancer cells can be largely attributed to horizontal gene transfer (genetic material that is shared between cells of the same generation). In fact, beneficial mutations do not enable cancer resistance. This breakthrough shows that cancer cells have built-in mechanisms that are actively used against treatments such as chemotherapy and radiation, meaning that characteristics of resistance can be associated with: “(1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation” [1]. These mechanisms include the modification of DNA and metabolic activity to render a previously used method ineffective. Therefore, it is crucial to use a variety of treatment methods such as surgery, radiotherapy, and chemotherapy, instead of limiting a patient to just one [3].
Extensive research in resistance to cancer treatment shows that the key to preventing cancer from becoming permanently resistant is anticipating its response to a treatment. Through anticipation and the wide range of treatments now available in the booming pharmaceutical industry, doctors may utilize a potent treatment program for cancer patients. In fact, advances in the pharmaceutical industry provides for more sophisticated treatment methods, allowing cancer patients to survive much longer. Ultimately, the discovery of these mechanisms in cancer cells encourages our treatment program to stay ahead of cancer cells before they are allowed to express permanent resistance.
References:
- Cree, Ian A., and Peter Charlton. 2017. “Molecular Chess? Hallmarks of Anti-Cancer Drug Resistance.” BMC Cancer. 17: 10. PMC. Web. 12 Feb. 2017.
- Holohan, Caitriona, et al. 2013. “Cancer drug resistance: an evolving paradigm.” Nature Reviews Cancer . 13.10: 714-726.
- Pastan, Ira, and Michael Gottesman. 1987. “Multiple-drug resistance in human cancer.” New England Journal of Medicine. 316.22: 1388-1393.