Monday, January 13, 2020

Cancer growth in the body could originate from a single cell – target it to revolutionise treatment

Cancer remains a frightening and largely incurable disease. The toxic side effects of chemotherapy and radiation make the cure often seem as bad as the ailment, and there is also the threat of recurrence and tumour spread.

Cancer treatment still follows a practically medieval method of cut, burn or poison. If the growth can’t be cut out through surgery, it may be burnt away with radiation or poisoned by chemotherapy. As a result, cancer therapy remains a daunting diagnosis for patients and treatment options seem limited for a disease which causes one in six deaths globally.

The failure to innovate in cancer treatment may lie in the very poor success rate of clinical trials. Approximately 95%-98% of new anti-cancer drugs actually fail phase III clinical trials, the phase in which new treatments are compared with existing therapy options. This is a staggering statistic. No other business could possibly survive with such an abysmal success rate.


 Chemotherapy and radiotherapy are broad-based treatments which attack the bulk of cancer cells but also damage healthy tissue. 


Most drugs are made to target “bulk” cancer cells, but not the root cause: the cancer stem cell. Cancer stem cells, also known as “tumour-initiating cells”, are the only cells in the tumour that can make a new tumour. New therapies that specifically target and eradicate these cancer stem cells are needed to prevent tumours growing and spreading, but for that there needs to be more clarity around the target.

Our new research may have discovered such a target. We have identified and isolated cells within different cancerous growths which we call the “cell of origin”. Our experiments on cancer cells derived from a human breast tumour found that stem cells – representing 0.2% of the cancer cell population – have special characteristics.


They generate vast amounts of energy and proliferate rapidly. We believe that they resemble the cancer cell of origin that has escaped senescence – the natural process of cell ageing and “death” which concludes a healthy cell life cycle. These are thought to be the first cancer cells which start the process of uncontrolled cell multiplication and cause tumours to form.

These cancer stem cells undergo anchorage-independent growth, also known as growth in suspension, without any tissue attachment. This is how metastasis occurs – spreading via the blood vessels and lymphatic vessels. These features put them front and centre as a new target for anti-cancer therapy.
 

Cancer stem cells grow in suspension in the bloodstream and spread throughout the body. 

With astonishing luck, these energetic cancer stem cells are colour-coded which means they have a natural phosphorescent glow, making them easy to identify and target.

Now that we have found them and we know how they behave, it should be relatively simple to find drugs to target cancer stem cells. In our new paper we have already shown that they are easily targeted with a mitochondrial inhibitor or a cell cycle inhibitor such as Ribociclib, an FDA-approved drug in the US which would prevent their proliferation.

Ultimately, this means that if we focus on energetic cancer stem cells, we may be able to directly hit the target. We might be able to turn cancer into a manageable chronic disease, like diabetes. We believe that we have arrived at the start of a new, more fruitful, road in cancer therapy. As a consequence, “big pharma” drug screening should actually focus on cancer stem cells and their relevant targets.


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Tuesday, November 21, 2017

Scientist find end-around method to stop triple-negative breast cancer

A team of scientists has found a new target for triple-negative breast cancer.

Triple-negative breast cancer, which is a particularly aggressive and difficult-to-treat form, earns its name because, unlike other breast cancer subtypes, its cells test negative for estrogen and progesterone receptors, as well as for a gene called HER2. Therefore, it cannot respond to therapies that inhibit cancer-growing signals that come from estrogen, progesterone and HER2.

The only treatment options for triple-negative breast cancer are surgery, radiation therapy and chemotherapy, each of which cause difficult side effects and rarely lead to remission.

Triple-negative breast cancer is also highly variable from patient to patient and even among tumour cells of a single patient, making it difficult to understand and treat. Other breast cancer subtypes are homogeneous, more predictable and treatable.

The researchers are working to study this variability and find an end-around method to stop triple-negative breast cancer, by seeking out unknown or little-understood routes toward shutting down uncoordinated growth.

"We're interested in the variability that's characteristic of triple-negative breast cancer," said the author . "We believe this variability gives clues to how the cancer arises, and clues to treatment possibilities that would exploit the way the tumors are regulated or misregulated as the cells communicate with each other.

The study detailed a possible way to reengage a tumor suppressor protein - Growth Differentiation Factor 11, or GDF11, that they found to be inactivated in triple-negative breast cancer cells.

"Instead of trying to find and target hormones or genes that might promote growth of these tumor cells, as has been successful for other cancer types, we are focusing on a protein in triple-negative tumor cells that normally should inhibit abnormal cell growth, but has been disengaged," he said.

Researchers have found that GDF11 does not mature properly into a bioactive tumor suppressor, as it should normally do, but instead accumulates within cells in a "pre-active" state.

"This is an exciting realization," he said, "because we now can look for ways to remobilize the GDF11 precursor and reengage its normal tumor suppressive activity wherever triple-negative cancer cells reside in the body.

"We're still early in this investigation, but it may be a step in the right direction for getting a handle on ways to target this very difficult to treat breast cancer subtype."


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