Improvements in cancer treatment: chemotherapy

By Naveesha Karunanayaka

Cancer is a major cause of death around the world with approximately 1 in 6 deaths caused by cancer.¹ Cancer is caused by unimpeded cell division and there are various methods to treat it, but these can cause disadvantageous effects to normal cells due to poor selectivity.

Chemotherapy, which is a cell cycle dependant treatment, causes programmed cell death. It uses cytotoxic chemicals, which are toxic drugs to living cells, as they act by causing cell death or preventing cell growth.² For example, alkylating agents cause DNA damage, impeding cell replication, and eventually resulting in cell death. On the other hand, antimetabolites, start at the root of the problem by inhibiting DNA synthesis.³ Standard chemotherapy weakens the body, causing greater damage than the cancer itself. However, “chemotherapy is still the regimen of choice for systemic treatment of almost all cancer types.”.³

The treatment comes with several issues, one being drug resistance, which is either a pre-existing condition or developed during treatment. This is often overcome by using “higher doses or greater frequencies of chemotherapeutic agents” with the aim to increase toxicity to cells.⁴ This is problematic since this increases damage to healthy cells, pushing the patient into a fragile state, emotionally and physically, making them susceptible to other diseases. An example of this is COVID-19, where it was found in a study that cancer patients had approximately a 5 times greater risk of developing severe complications compared to patients without cancer. Another issue to consider is the different effects cancer treatment may have between men and women. Studies have shown that men and women have ‘significant differences’ in side effects from chemotherapy.⁵ This highlights the importance of the specificity of the treatment, regarding the aim to attack the cells and gender wise.

Using chemotherapy comes with well-known effects on patients, but some lesser-known impacts on the environment. Chemotherapeutic drugs known as antineoplastic agents or cytostatic drugs are used in treatments for a variety of cancers. Different levels of these toxins enter the aquatic environment because remnants of the drugs are ineffectively filtered from human excretion during wastewater treatment. These drugs in treatment stop the growth and division of cells but when released into the environment, they affect the ecosystem by altering fertility of animals and causing increased genetic defects.⁶

Chemotherapy is currently evolving and is at a crossroads, it is being altered to become more specific to tumour cells rather than healthy cells. It is now considered an ‘adjuvant therapy’ and is primarily used for its toxicity.⁷ Meanwhile, improvements in patient susceptibility and resistance are being explored through microfluidic chips and artificial intelligence (AI), which will help avoid overly toxic therapies and prevent extensive damage during treatment. Machine learning techniques such as Artificial Neural Networks (ANNs) and Decision Trees (DTs) allow for more accurate decision-making when diagnosing and treating cancers, helping find the best location for treatment for each patient. Applying this technology to microfluidic devices allows observation of the reaction of a patient’s tumour cell to a certain chemotherapeutic drug prior to it being used in a patient, improving treatment, as drug’s effects can be observed and analysed before any invasive procedure.

Advancements are also being made in the field of nanorobotics, to use as cancer treatment. The nanorobot consists of two elements, targeting and therapeutic parts. According to Spelkov et al., the targeting ‘detects pathogenic cells’ which recognises incorrect RNA and binds to it ‘introducing a chemically modified oligonucleotide’ which is then cleaved, ‘and a fluorescence occurs’.⁸ The therapeutic part of the device ‘destroys the pathogenic RNA strand’ and the more RNA that is destroyed, the less harmful proteins are produced, and thus reducing the ability of the tumour to grow.⁸ These nanorobots use sensory equipment to travel to a precise location via internal or external stimuli, which can range from pH or temperature changes to an ultrasound field.⁹

Overall, cancer is a long battle, but technology is constantly improving and within the next decade it can be expected that chemotherapy will be placed on the back burner while new emerging treatments will be used. These will attempt to use AI and Machine learning, as well as specificity when using drugs in therapy. Developments in recognising tumour cells exclusively and reducing drug resistance will allow great advancements in cancer treatments and help overcome one of society’s leading causes of death.

References:

1. American Cancer Society. Global Cancer Facts & Figures 4th Edition. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/global-cancer-facts-and-figures/global-cancer-facts-and-figures-th-edition.pdf [Accessed 21st June 2021]
2. Cheok C. Protecting normal cells from the cytotoxicity of chemotherapy. Cell Cycle. 2012;11(12): 2227-2227. Available from: doi:10.4161/cc.20961  
3. Lilienthal I, Herold N. Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies. International Journal of Molecular Sciences. 2020;21(18): 6885. Available from: doi:10.3390/ijms21186885
4. Wei G, Wang Y, Yang G, Wang Y, Ju R. Recent progress in nanomedicine for enhanced cancer chemotherapy. Theranostics. 2021;11(13): 6370-6392.
   Available from: doi:10.7150/thno.57828
5. Cancer Treatment Centers of America. Study: Men and women may experience
   different side effects from chemotherapy. Available from: https://www.cancercenter.com/community/blog/2020/06/men-women-chemotherapy [Accessed 13^th June 2021]
6. European Commission – CORDIS. Fate and effects of cytostatic pharmaceuticals in the environment and the identification of biomarkers for and improved risk assessment on environmental exposure. Available from: https://cordis.europa.eu/article/ id/90772- the-environmental-dangers-of-anticancer-drugs [Accessed 11^th June 2021]
7. Chew H K. Adjuvant therapy for breast cancer: who should get what? The Western Journal of Medicine. 2001;174(4): 284–287. Available from: doi:10.1136/ewjm.174.4.284
8. Spelkov A A, Goncharova E A, Savin A M, Kolpashchikov D M. Bifunctional RNA-Targeting Deoxyribozyme Nanodevice as a Potential Theranostic Agent. Chemistry Europe. 2020;26(16): 3489-3493. Available from: doi:10.1002/chem.201905528
9. Soto F, Wang J, Ahmed R, Demirci U. Medical Micro/Nanorobots in Precision Medicine. Advanced Science. 2020;7(21). Available from: doi:10.1002/advs.202002203.