{"id":2234,"date":"2022-12-09T13:21:14","date_gmt":"2022-12-09T13:21:14","guid":{"rendered":"https:\/\/horizon.peachpuff-wolverine-566518.hostingersite.com\/?p=2234"},"modified":"2022-12-09T13:21:14","modified_gmt":"2022-12-09T13:21:14","slug":"breast-cancer-an-aggressive-variant-triggers-a-hunt-for-cures","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/horizon\/2234\/breast-cancer-an-aggressive-variant-triggers-a-hunt-for-cures\/","title":{"rendered":"Breast cancer: an aggressive variant triggers a hunt for cures"},"content":{"rendered":"

Triple negative breast cancer is a hard-to-treat form that accounts for 15% of all cases, with recovery hopes emerging from chemotherapy drugs that stimulate the immune system and others that cause tumour cells to implode.<\/p>\n

By<\/em><\/strong>\u00a0\u00a0VITTORIA D\u2019ALESSIO<\/p>\n

Breast cancer is the most common type in women and, in Europe alone, causes almost\u00a092 000 deaths a year<\/a>. Though this number is undoubtedly high, survival rates are improving. Advances in prevention, detection and treatment mean a patient now has a\u00a090% chance of survival<\/a>.<\/p>\n

But one particularly aggressive variant is bucking the trend: triple negative breast cancer (TNBC), so named because it lacks three kinds of cell proteins. Tumours in this category account for around 15% of breast-cancer cases and the outlook is far worse than for other types.<\/p>\n

Triple trouble<\/strong><\/p>\n

Tumours grow faster, spread more often before being discovered and are likelier to come back after treatment. And when TNBC does recur in other organs, an early death is likely, with\u00a0survival rates as low as 11%.<\/a><\/p>\n

Currently, no specific treatment exists for TNBC. The response usually involves surgical removal of the tumour followed by a cocktail of chemotherapy drugs that are known to work against other types of cancer. Often, however, the results are patchy and temporary.<\/p>\n

\u2018After some time, the body often creates defences against this cocktail and it no longer works,\u2019 said Dr Andreia Valente, co-coordinator of an EU-funded project to find cures for TNBC. \u2018When this happens, the tumour usually becomes multi-drug resistant, meaning it doesn\u2019t respond to any other type of chemotherapy treatment, and the cancer then becomes very aggressive.\u2019<\/p>\n

Dr Valente, who works at the University of Lisbon in Portugal, and her research partner Dr Helena Garcia coordinate\u00a0CanceRusolution<\/a>, a one-year\u00a0Women TechEU<\/a>\u00a0initiative running until end-May 2023.<\/p>\n

Rare metal<\/strong><\/p>\n

Efforts are focused on ruthenium, a rare, silvery-white metal known to be well-tolerated by the human body. From early experiments, it appears that the ruthenium-based drug the project team has developed both halts the growth of TNBC cells and stops them from spreading.<\/p>\n

A second round of trials, this one on animals, is due to start soon. Alongside these, the researchers will be analysing the drug\u2019s safety profile to ensure it is toxic to cancer cells but harmless to the rest of the body.<\/p>\n

Chemotherapy is notorious for its brutal side-effects \u2013 ranging from nausea and lack of appetite to exhaustion and hair loss \u2013 because drugs that attack the fast-growing cells of a tumour typically kill healthy cells too.<\/p>\n

Early results from CanceRusolution suggest a drug based on ruthenium would cause fewer side-effects in patients because healthy cells seem to be unaffected.<\/p>\n

\u2018So far, from a toxicity point of view, the drug\u2019s profile looks good,\u2019 said Dr Garcia. \u2018Our studies show that 24 hours after administering the drug, there\u2019s a high concentration of the compound in the tumour, but in the surrounding blood and urine it\u2019s almost gone. This means the secondary effects of our drug should be low.\u2019<\/p>\n

Cell traits<\/strong><\/p>\n

A healthy breast cell is packed with receptors \u2013 proteins expressed on the surface of the cell. They allow it to respond to hormones (for instance, by enlarging during pregnancy) and other vital molecules involved in controlling how the cell grows, divides and repairs itself.<\/p>\n

Most cancer cells also possess receptors. To make an accurate diagnosis, a clinician will analyse a sample of diseased breast tissue to discover which receptors \u2013 known as biomarkers in this context \u2013 are being expressed.<\/p>\n

Three biomarkers are commonly found in breast tumours and drugs have been developed to target all three.<\/p>\n

But TNBC is an outlier. It possesses none of these biomarkers and, as a result, provides no obvious pathway to sabotage tumour growth.<\/p>\n

Trojan-horse approach<\/strong><\/p>\n

The drug developed by the team in Portugal gets around this problem by delivering the drug as a nanoparticle that enters the tumour through defects in the tumour\u2019s blood-supply system. Once inside, it cracks open, Trojan-horse style, to release the active ingredient.<\/p>\n

This targets a completely different component of TNBC cells \u2013 the cytoskeleton: the complex network of interlinking protein filaments that fills the cell\u2019s interior and acts as scaffolding.<\/p>\n

\u2018The drug then destroys the foundations of the cell,\u2019 said Dr Garcia. \u2018Without a functioning cytoskeleton, the cell has no way of surviving. It splatters.\u2019<\/p>\n

With new funding, the researchers believe their drug could be ready for evaluation in humans within two years.<\/p>\n

Diverse group<\/strong><\/p>\n

Thinking of TNBC as a single type of breast cancer is an oversimplification. It is in fact a highly diverse group of cancers.<\/p>\n

Researchers, however, lack a classification of subtypes. Having one would allow them to zero in on new biomarkers that, it is hoped, would pave the way for new tailored treatments.<\/p>\n

Classifying patients according to the precise character of their tumour, and seeking new targets for TNBC treatments, are pillars of another EU-funded project \u2013\u00a0P70-IMMUNEBREAST<\/a>.<\/p>\n

After studying 350 cancerous tissue samples, the project\u2019s researchers have devised a classification system based on how much \u2018kinase\u2019 \u2013 an enzyme and another cancer biomarker \u2013 is expressed by a tumour.<\/p>\n

Earlier research showed that one particular kind of kinase, P70S6K, is found in high levels in TNBC tumours.<\/p>\n

\u2018What we\u2019re interested in is the link between this kinase and the body\u2019s immune response,\u2019 said researcher Dr Rebeca Jimeno. \u2018Tumours develop in our bodies and \u2013 when all goes well \u2013 our immune system recognises them and destroys them.\u2019<\/p>\n

The big question is why this system sometimes fails.<\/p>\n

Immunity angle<\/strong><\/p>\n

Dr Jimeno, who is based at the Spanish National Cancer Research Centre, has found that when high levels of P70S6K kinase are expressed, fewer B cells are found in a tumour.<\/p>\n

B cells recognise, infiltrate and finally destroy cancer cells. In other words, P70S6K allows cancer to hide from the immune system and grow undisturbed.<\/p>\n

One of the next research steps is to find an appropriate inhibitor for this kinase.<\/p>\n

\u2018Drugs are being tested, but I suspect it will be some years before one is found that\u2019s well-tolerated by the body,\u2019 said Dr Jimeno.<\/p>\n

She is hopeful that a cure will eventually be found.<\/p>\n

\u2018We\u2019re trying so hard to find a solution for this unmet need, and I\u2019m confident that one piece of research at a time, we\u2019ll get there,\u2019 said Dr Jimeno.<\/p>\n

Research in this article was funded via the EU\u2019s Marie Sk\u0142odowska-Curie Actions (MSCA). This material was originally published\u202fin <\/em>Horizon<\/em><\/a>, the EU Research and Innovation Magazine.\u202f\u00a0<\/em><\/p>\n

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