Two student researchers at Weill Cornell Medicine-Qatar (WCM-Q) have recently published their paper in the prestigious scientific journal, Cancers.

Their paper discusses the capacity of naturally occurring plant compounds to alleviate nerve damage and pain caused by anti-cancer drugs.

Research project on flavonoids

Students Manaal Siddiqui and Basma Abdellatif were sophomore pre-medical students at WCM-Q when they began the research project to examine the capacity of flavonoids, which are found naturally in fruits, vegetables, flowers and barks, to alleviate chemotherapy-induced peripheral neuropathy (CIPN).

CIPN is a debilitating and life-limiting condition characterised by damage to the peripheral nerves, a side-effect of potent and often life-saving chemotherapy drugs. This nerve damage means sufferers can experience severe pain, numbness, uncomfortable tingling sensations, weakness, cramps, difficulty walking, hearing loss, and problems with precise hand control, among other symptoms.

Guided by their research mentor at WCM-Q, Dr Dietrich Büsselberg, Siddiqui and Abdellatif conducted a painstaking systematic review of a vast quantity of existing research into the effects of flavonoids on CIPN. They then synthesized and presented the data alongside detailed descriptions of the intricate chemical mechanisms by which chemotherapy drugs cause pain and peripheral nerve damage and how flavonoids can inhibit these mechanisms.

The two are now in their first year of the Medical Program at WCM-Q and are delighted when their paper, titled ‘Flavonoids Alleviate Peripheral Neuropathy Induced by Anticancer Drugs’, was published in Cancers.

Flavonoids and CIPN

The mechanisms by which chemotherapy drugs cause nerve damage are varied and include pro-inflammatory cytokine release (inflammation), oxidative stress (an imbalance between harmful free radicals and beneficial antioxidants), ion channel activation (a disturbance in the way molecules move in and out of cells), and damage to the mitochondria, which generate chemical energy to power the cell’s biochemical reactions.

According to Siddiqui, the research shows that flavonoids can be beneficial, but is more complex than it might seem at first glance. This is because there are many different kinds of flavonoids, many different chemotherapy drugs and there are different types of neuropathy, and they all interact in different ways.

This means there are many, many different mechanisms at work when we talk about flavonoids helping to relieve CIPN. We took a comprehensive approach to try to understand and present the data about as many of these interactions as we possibly could.

Since CIPN gets worse with increasing doses of anti-cancer drugs, the condition is the leading cause of premature chemotherapy cessation, leading to reduced lifespan. Moreover, peripheral neuropathy itself is associated with an increased risk of early death in adults. It is estimated that around 40% of people treated with chemotherapy drugs develop CIPN. Some treatments employed to manage CIPN include steroids, anti-depressants, numbing medications and anti-seizure medications such as gabapentin and pregabalin.

None of these treatments provides a truly satisfactory way to alleviate the symptoms of CIPN, and all cause undesirable side effects. Some flavonoids modulate the mechanisms by which anti-cancer drugs cause CIPN. As such, they could potentially be used to help to reduce the negative side effects of anti-cancer drugs.

Abdellatif said they were interested in this area because CIPN affects a large proportion of people who receive chemotherapy treatment for cancer.

She said that chemotherapy drugs can be very effective at saving people’s lives, but as medical practitioners, they also have to think about the patients’ quality of life and how to improve it. She said they were excited by the idea that flavonoids could potentially contribute to this in a significant way.

We thought that compiling all available data in a single research project could help other investigators realise the potential for using flavonoids to help relieve pain for CIPN sufferers.

The other authors of the research paper are Dr Büsselberg, second-year pre-med student Kevin Zhai, and Alena Liskova and Peter Kubatka of Comenius University in Bratislava, Slovakia.

Dr Büsselberg said Siddiqui and Abdellatif showed great professionalism and ability as researchers to produce an excellent paper that provides a truly comprehensive reference source for other researchers.

The hope is that this will provide research targets to guide the development of new, more effective therapies for alleviating CIPN, which would be enormously beneficial to cancer patients. For this reason, we are very pleased that the study is published in an open-access journal.

The research was supported by a National Priorities Research Program grant from Qatar National Research Fund and by the Biomedical Research Program at WCM-Q.

You can read the paper in full via this link. Visit qatar-weill.cornell.edu for more information about WCM-Q.  


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