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What’s worse than having cancer?

An overview of the biological link between cancer and depression (and how to win the chess match against them both).

There is a silent but brutal accomplice to cancer, which dramatically affects the lives of those who are affected.

Depression frequently co-occurs in cancer cases. But it is not just due to the emotional distress of having a life-threatening disease. A common biological mechanism seems to underpin this comorbidity.

A recent article by our group reviewed the scientific literature on the link between cancer and depression, highlighting the effect of this common biological mechanism: inflammation, and a specific aspect of inflammation called the ‘kynurenine pathway’.

Here I will take cues from our paper to explore the reasons behind this comorbidity and the clinical implications of this intricate chess match between us — patients, clinicians, and researchers — and the combined force of cancer and depression.

Cancer and Depression

Cancer patients are a population at high-risk for the development of depression, with overall higher prevalence rates than those observed in the general population.

Cancer, with all its more than 100 subtypes, could affect almost every part of the body, with different symptoms and prognoses. It is often unpredictable, sometimes rapidly lethal, and the therapies are highly invasive and not always effective.

Its potential to invade the whole body, along with the visible signs of the illness and the challenging treatments, contribute to the ever-lasting fears about it.

It’s quite clear to everyone that receiving a diagnosis of cancer could be enough to feel down and to lower your mood. However, not every person diagnosed with cancer is clinically depressed, that is, has a clinical condition that is more than being sad and worried about one’s health status.

The detrimental effects of these two diseases — cancer and depression — do add up, especially when they occur together, impacting the life of those who are affected, and of their relatives.

The role of inflammation and implications for treatment

In the last few decades, we have understood more about the role of inflammation in the pathophysiology of both cancer and depression.

Inflammation is, on a basic level, a response of our body to potential threats (such as illnesses), that involves the activation of the immune system.

Cancer is associated with immune abnormalities, and inflammation is pivotal in cancer development. Inflammation is also caused by cancer therapies, especially chemotherapy, in an often-unfavourable alliance between cancer and its treatment.

Depression is also linked to inflammation: depressive symptoms are frequent when the immune system is activated, and many depressed patients have high inflammation.

It is therefore particularly intriguing to look at depression in illnesses that are also characterized by high inflammation — like, indeed, cancer.

If the high prevalence rates of depression in cancer is due to the immune activation, fighting inflammation could also prevent the development of depression.

Depression is not an easy-to-treat disorder and the limits of the current antidepressant therapies are well known to clinical practitioners. About one third of depressed patients have inadequate responses to treatment. This reveals an urgent need for new approaches in treating depressive disorders.

If inflammation is elevated in at least some depressed patients — for example, patients with cancer — than anti-inflammatory treatments could be helpful. But which anti-inflammatories? Which bits of inflammation are important in causing depression?

One inflammation-related pathway that appears to be dysregulated in both cancer and depression, is the kynurenine pathway.

This is a metabolic process in which the essential amino acid tryptophan is converted into substances that are toxic for the brain and can induce depression.

The activation of the kynurenine pathway during cancer may therefore be crucial to the development of depression, even though further research is needed to disentangle its exact role.

Is this going to deliver new antidepressant drugs?

It is probably too early to say, although drugs exist that inhibit the key enzyme of kynurenine pathway, indoleamine 2,3-dioxygenase (IDO). Many trials have been performed on IDO inhibitors in cancer, although with conflicting results, and some IDO inhibitors have shown promising results in association with classical anticancer therapies.

Nevertheless, at this stage of research, the potential efficacy of IDO inhibitors in treating depression during cancer is still only a hypothesis.

However, one thing is clear: to win the chess match against cancer, we really will need to fight against both cancer and depression.

Targeting inflammation might be just such a strategy to win the match — especially if we can develop a more precision medicine approach in this field, identifying those patients who will benefit from anti-inflammatory interventions.

image source: pxhere


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