Self-assembling Molecules Asphyxiate Cancerous Cells

Calendar September 9, 2022 | Posted by admin

Treatment of cancer is a long-term process because remnants of living cancer cells often evolve into aggressive forms and become untreatable. Hence, treatment plans often involve multiple drug combinations and/or radiation therapy in order to prevent cancer relapse. To combat the variety of cancer cell types, modern drugs have been developed to target specific biochemical processes that are unique within each cell type.

However,  are highly adaptive and able to develop mechanisms to avoid the effects of the treatment.

“We want to prevent such adaptation by invading the main pillar of cellular life—how cells breathe—that means take up oxygen—and thus produce  for growth,” says David Ng, group leader at the MPI-P.

The research team produced a synthetic drug that travels into cells where it reacts to conditions found inside and triggers a chemical process. This allows the drug’s molecules to bind together and form tiny hairs that are a thousand times thinner than . “These hairs are fluorescent, so you can look at them directly with a microscope as they form,” says Zhixuan Zhou, an Alexander-von-Humboldt-fellow and first author of the paper.

The scientists monitored the oxygen consumption in different cell types and found that the hairs stop all of them from converting oxygen into ATP, a molecule that is responsible for energy delivery in cells. The process worked even for those cells derived from untreatable metastatic cancer. As a result, the cells die rapidly within four hours. After some more years of research, the scientists hope that they can develop a new method to treat up-to-now untreatable cancer.

Weil, Ng and colleagues have shown an exciting outcome under controlled laboratory culture and will continue to unravel deeper insights on the basis of how these  prevent the conversion of oxygen to chemical energy. With further development, these objects could in the future possibly also be manipulated to control other cellular processes to address other important diseases.

They have published their results in the Journal of the American Chemical Society.

Source: https://phys.org/

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Light-activated Immunotherapy Kills Brain Cancer

Calendar June 21, 2022 | Posted by admin

Scientists at the Institute of Cancer Research in London have developed a new light-activated “photoimmunotherapy” that could help treat brain cancer. The key is a compound that glows under light to guide surgeons to the tumor, while near-infrared light activates a cancer-killing mechanism.

The new study builds on a common technique called Fluorescence Guided Surgery (FGS), which involves introducing a fluorescent agent to the body which glows under exposure to light. This is paired with a synthetic molecule that binds to a specific protein, such as those expressed by cancer cells. The end result is tumors that glow under certain lighting conditions or imaging, guiding surgeons to remove the affected cells more precisely.

For the new study, the researchers gave the technique an extra ability – killing the cancer as well. They added a new molecule that binds to a protein called EGFR, which is often mutated in cases of the brain cancer glioblastoma. After the fluorescence has helped surgeons remove the bulk of the tumor, they can shine near-infrared light on the site, which switches the compound into a tumor-killing mode by releasing reactive oxygen species. The idea is to kill off any remaining cells that could – and often do – stage an aggressive comeback after surgery.

In tests in mice with glioblastoma, the researchers showed that animals treated with the new technique had clear signs of tumor cell death in as little as one hour after exposure to near-infrared light. On top of that, the treatment also caused the animals’ immune systems to mount a new attack on the cancer, which could help reduce the chances of relapse.

“Our study shows that a novel photoimmunotherapy treatment using a combination of a fluorescent marker, ‘affibody’ protein and near-infrared light can both identify and treat leftover glioblastoma cells in mice,” said Dr. Gabriela Kramer-Marek, lead author of the study. “In the future, we hope this approach can be used to treat human glioblastoma and potentially other cancers too.”

The team says the technique could also eventually be used to treat other types of cancer. The research was published in the journal BMC Medicine.

Source: https://www.icr.ac.uk/
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https://newatlas.com/

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Drug Prevents Breast Cancer Recurrence and Metastasis

Calendar May 24, 2022 | Posted by admin

Even when detected early, some cancers are more aggressive and more fatal than others. This is the case, for example, with triple negative breast cancer which accounts for 10 to 15% of all breast cancers. This cancer affects 1,000 patients per year in Belgium, while the figure worldwide is 225,000. Around half of the patients will develop local recurrences and metastases, regardless of the treatment they receive. No specific treatment is currently capable of preventing these two events. Patients suffering from pervasive triple negative breast cancer have only a one-in-ten chance of a cure. In 2014, Pierre Sonveaux, a researcher at the University of Louvain (UCLouvain) Institute for experimental and clinical research, succeeded in demonstrating the principle that it was possible to prevent the appearance of melanoma tumour metastases in mice. However, the experimental molecules used at the time were far from being drugs.

Since then, the UCLouvain researcher and his team, including post-doctoral researcher Tania Capeloa, have continued their work thanks in particular to sponsorship obtained by the UCLouvain Foundation. They have now succeeded in establishing that a drug developed for diseases other than cancer, MitoQ, avoids the appearance of metastases in 80% and local recurrences of human breast cancer in 75% of cases in mice. Conversely, most of the mice not treated suffered a recurrence of their cancer, which spread.

To do this, the researchers treated mice affected by human breast cancer. They treated them as hospital patients are treated, i.e. by combining surgery with a carefully dosed cocktail of standard chemotherapies. However, the UCLouvain researchers supplemented this standard treatment with the new molecule, MitoQ. They not only demonstrated that the administration of MitoQ is compatible with standard chemotherapies, but also that this innovative treatment prevents both relapses and metastases of breast cancer in mice. “We expected to be able to block the metastases, says Pierre Sonveaux enthusiastically. But preventing the recurrence of the cancer was totally unexpected. Getting this type of result is a huge motivation for us to carry on.” In short, this is a giant step given that the three main causes of cancer mortality are recurrences, the spread of the cancer caused by metastasis and resistance to treatment. And that there is currently no other known molecule capable of acting like MitoQ.

How does it work? Cancers consist of two types of cancerous cells: those that proliferate and are sensitive to clinical treatments and those that are dormant and that bide their time. Such cells are more harmful. The problem? These cancerous stem cells are resistant to clinical treatments. They result in metastases and if, unfortunately, cancer surgery fails to remove them all, they cause recurrences. These relapses are currently treated using chemotherapy. However, this tends to be relatively ineffective owing to the resistance to treatment developed by the tumorous cells . This is where the important discovery of the UCLouvain scientists comes in: the molecule MitoQ stops cancerous stem cells from awakening.

What next? MitoQ has already come through the first clinical phase successfully. It has been tested on healthy patients, both men and women, and proves to be only slightly toxic (nausea, vomiting). In addition, its behaviour is known. What next? The discovery made by the UCLouvain scientists opens wide the path for the clinical 2 phase, intended to demonstrate the efficacy of the new treatment in cancer patients.

Source: https://uclouvain.be/
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