Sunday, January 29, 2012

Drug kills most difficult-to-treat cancer cells

Not all tumours are the same. Every cell has the potential to become cancerous and turn to rapid growth in order to create a full sized tumour. Some cells are more adept than others: if a tumour arises from a stem cell, it is often harder to treat than a cancer derived from adult cells from a specific tissue. So-called cancer stem cells are the most difficult to treat because they are hard to eradicate with drugs, and can easily reform into a tumour even if only a few cells remain. In some cases, only a few cancer stem cells are the driving force between tumour growth. The problem is that stem cells naturally function by replenishing tissues and self-renewal. It means we need a more aggressive treatment to get rid of them when they turn malicious. Chinese researchers may have found the answer.

Stem cells have a unique feature called pluripotency. That means they can differentiate into various tissues, because of their primitive nature. It means we want to develop new therapies that focus on this specific capability. Chinese scientists created chemicals that specifically target these cells in tumours, which they hope to use in order to eradicate the most difficult to treat cancer cells. According to them, it is the first set of drugs that can be used to specifically focus on the 'mothers' of all cancer cells.
A simple representation of cancer stem cells (yellow).
To be precise, the aforementioned chemicals target a molecule called LSD1. It is specific for primitive cells that have the capability to differentiate into many forms of tissues. LSD1 works by resetting chemical modifications found on DNA. We needs these chemical modifications to shut off large parts of the DNA: different tissues need a different set of genes being expressed, and because every cell possesses the same genome, each tissue type needs a specific set of modifications to stop parts of the DNA being expressed. Stem cells however, need to have a fairly pristine genome in order to create all the tissues possible. That is where LSD1 comes in: it removes so-called methyl groups that 'silence' the DNA. Naturally, when LSD1 is inhibited, stem cells cannot keep their primitive character. This field of research is called epigenetics and has already been implied in cancer.

Stem cell treatment
Because stem cells constantly renew themselves and are tasked with replenishing tissues, they are inherently risky to use in treatment. They can easily lose control and contribute to tumour formation. This is clearly visible in stem cell treatment, where injected cells do not do the job they are supposed to do, but instead contribute to a wide variety of cancers. Because they have the potential to become all possible forms of tissue, it means they can do the same with tumours. According to the Chinese scientists, their LSD1 inhibitors not only work in naturally developed cancers, but also in stem cell treatment, which could make this form of therapy safer. We use stem cells for many experimental therapies, such as restoring a damaged spinal cord.

Clinicians would be able to use the LSD1 inhibitors in a cocktail  of cancer drugs. If they work, they should make tumours better treatable and reduce the number of metastasis or recurrence. However, the Chinese scientists did not show any experimental results of their chemicals: they simply stated that LSD1 inhibitors showed efficacy towards cancer stem cells. Of course, animal studies followed by clinical trials are needed to assess its true clinical potency. Nevertheless, it is an important discovery in oncology, as it allows us to target the nastiest malicious cells our body can produce. 

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