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|| New Research Finds Mechanoresilient Cancer Cells Can Withstand Mechanical Stress and Are More Proliferative and Drug Resistant ||

|| Sunday: September 24: 2023 || ά. Scientists discovered that ‘mechanoresilient’ cancer cells, those can withstand significant mechanical stress, are more proliferative and drug resistant. The ability of cancer cells to metastasise or spread from one part of the body to another, is one of the reasons why cancer can be extremely challenging to treat. However, the process, that drives metastasis is complex and not fully understood. In a recent Study, scientists from the National University of Singapore:NUS have tried to look deeply at the complex interactions between tumour cells and the micro-environment and showed that some cancer cells are resilient to mechanical stress and such cells, also, have a stronger ability to multiply rapidly to form secondary tumours.

“Understanding how some cancer cells can survive mechanically-induced cell death is key to preventing the spread of malignant tumours and paves the way for more targeted therapies.” Said the Lead Author of the research Professor Lim Chwee Teck, who is the Director of the NUS Institute for Health Innovation and Technology and holds an appointment at the Department of Biomedical Engineering under the NUS College of Design and Engineering. :::ω:::

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|| The European Union Funding For Natural Killer Cells That Fight Cancer ||



|| Thursday: September 21: 2023 || ά. As certain tumour cells are able to conceal themselves in the body, it, often, means that patients with aggressive cancers experience a recurrence of the cancer after treatment. By programming genetically modified killer immune cells to seek and destroy the hiding tumour cells and tumour stem cells, it is hoped that more effective treatment options can be developed.

An international research project, with key technologies, developed by Lund University in Sweden, will be used to advance immunotherapies for acute myeloid leukemia:AML, glioblastoma and pancreatic cancer. This consortium has been granted approximately 40 million SEK by EU’s key funding programme for research and innovation, Horizon Europe. Human physiologies have specialised immune cells, that specifically seek and destroy tumour cells. These cells are called natural killer cells. However, through specific mechanisms of selection, some tumour cells, including tumour stem cells, evade these killer cells and, indeed, the chemotherapeutic drugs and persist in the body. 

By genetically modifying the natural killer cells to increase their ability to target and destroy hiding tumour cells, the researchers propose that cancer therapies will be more effective. Niels-Bjarne Woods is a stem cell researcher at Lund University and leads the research team, that has, over the last decade, developed a system to produce a potentially unlimited supply of the killer immune cells, that can be tailored for genetic manipulation for cancer targeting.

The system produces the killer immune cells from induced pluripotent stem cells, which are regarded as an ideal source of cells, being able to unlimited supply of cells, which are conducive to the genetic manipulations they will perform.

“One of the factors we have identified for producing the natural killer cells from pluripotent stem cells is through regulating metabolism. Our cells contain mitochondria, that act as a mini power station for cell function. By feeding the mitochondria, we improve how the immune cells develop from the pluripotent stem cells.” Says Niels-Bjarne Woods.

Now, the research team at Lund University and its collaborative partners at Copenhagen University Hospital Denmark, Hannover Medical School in Germany and the bio-pharmaceutical company Amniotics AB Lund, have received a large grant from the European Innovation Counsel to develop this technology platform. The researchers will jointly investigate how killer cells can be tailored for the treatment of AML, glioblastoma or brain tumour and pancreatic cancer. These are all aggressive types of cancer with a very poor prognosis.

“The idea is not to replace existing cancer therapies, at least, not yet, but, rather to supplement these treatments with an effective power-clean-up of the remaining tumour cells, including tumour stem cells, that are difficult to remove and which lead to the recurrence of the disease. We have a panel of innovative technologies for how to achieved this, including one’s under development.” Says Niels-Bjarne Woods.

A possible treatment modality would be to transplant the specialised killer cells into cancer patients after their standard chemotherapy treatment but prior to a cancer relapse. This would ensure the higher ratio of effector killer cells per residual cancer cell to maximise the likelihood of permanent cancer ablation. || ΕΛ ||  ::::ω::::

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|| Prostate Cancer Patients at London Royal Free Hospital Get Access to a New Theranostic Treatment With Lutetium-177 PSMA ||



|| Thursday: September 07: 2023 || ά. Nine patients with advanced prostate cancer at the Royal Free Hospital:RFH are currently undergoing to benefit from a new highly targeted radiation treatment. Described as ‘theranostic’ treatment, this new therapy works by linking a radioactive particle to a molecular marker for the cancer in order to pinpoint the disease, while at the same time reducing damage to healthy cells.

While this treatment with Lutetium-177 PSMA has been designed, specifically, for prostate cancer, very similar treatment is already being used for patients with neuroendocrine cancer at the RFH. Clinicians say that theranostic approach is likely to be used more widely in the future for a number of other common cancers, as it is usually well tolerated, with fewer side effects compared to chemotherapy.

The treatment, given every six weeks, requires rigorous protocols to ensure staff safety as the patient becomes slightly radioactive for a short period of time. As soon as the treatment is delivered by injection into a vein in the arm the member of staff must immediately leave the lead-lined room. Patients can typically go home the same day but need to take some precautions at home for a couple of weeks while they remain radioactive. The particle is metabolised and the waste carried away in the patient’s urine.

Dr Mark Prentice, a Clinical Oncology Consultant for the Royal Free London, said, “The prostate patients, who are currently receiving theranostic treatment are as a result of an expanded access programme by the company, who manufactures it. However, it is currently being considered by The National Institute for Health and Care Excellence:NICE and we hope to be able to expand accessibility further, subject to approval. We have the clinicians and allied health professionals with the expertise in our nuclear medicine department to support our patients.

Currently the treatment is only available to patients with advanced disease, who have progressed through other lines of treatment but we are currently involved in trials, that are assessing the role of Lutetium-177 PSMA much earlier in a patient’s cancer journey.

At the moment the treatment is expensive but it should be possible to reduce costs over time. There are a lot of people involved, from physicists to pharmacists to consultants, technologists and nursing staff. But it is worth the effort because outcomes are good.”

Farhan Naim, Director of Research and Development at RFL, said, “It’s fantastic that, thanks to previous clinical trials carried out at the Royal Free London, our patients now have access to this expanded access programme, giving select patient groups the opportunity to benefit from this exciting and novel treatment. This is an important addition to therapeutic options for patients with cancer.” :::ω:::

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||  Breast Cancer: New Tools For Tackling It Well ||



|| Thursday: August 31: 2023 || ά. Breast cancer is the most common cancer in women. In Finland, around 5,000 women are diagnosed with breast cancer every year and one in eight women will get breast cancer at some point in their lives. However, the prognosis of a patient in Finland is one of the best in Europe: 85% of those with breast cancer will be alive ten years after the diagnosis.

Breast cancer is not one single disease but, a group of different subtypes. Based on the biological properties of the tumour, breast cancer is divided into luminal hormone-dependent breast cancer, HER2-positive breast cancer or triple negative breast cancer. Most cases of breast cancer are hormone dependent and slow-growing. In hormone-dependent breast cancer, there are hormone receptors on the surface of cancer cells to which the female hormones oestrogen and progesterone are bound, thus, contributing to cancer growth. 

This cancer type is the most common, usually, the slowest to progress and the one with best prognosis. In HER2 positive breast cancer, there is an abundance of HER2 growth factor receptors on the cell surface, promoting cancer growth. In triple negative breast cancer, there are no hormone or HER2 receptors on the cancer cell surface. HER2 positive and triple negative breast cancer are typically aggressive; however, HER2 positive breast cancer can nowadays be treated with effective precision drugs.

“HER2 antibodies have been a major improvement in the treatment of this type of cancer. More and more of them have been introduced in the past 05–10 years, and they are nowadays routinely used in treatment.” says Päivi Auvinen, Service Director and Chief of Department at the Cancer Centre of Kuopio University Hospital.

Breast cancer is primarily treated by surgery. When necessary, surgery is followed by radiation therapy and drugs, i.e., cytostatics, that destroy cancer cells and, depending on the cancer type, also, hormone therapy, that blocks the action of female hormones or, precision drugs. Sometimes, drug therapy is initiated already before surgery to, for example, improve tumour operability.

“For the treatment of HER2 positive breast cancer, for example, we have several new drugs whose effectiveness has been studied specifically before surgery, so they will be used in hospitals as neo-adjuvant treatment for larger or more widespread tumours. They are an interesting addition to treatment, although, actual comparative studies before versus after surgery are unfortunately scarce. The clinical impression nevertheless is that neo-adjuvant treatment would be associated with fewer cases of cancer recurrence.”

“Pre-surgery immuno-oncology, on the other hand, is bringing a significant change to the treatment of triple negative breast cancer. Previously, immuno-oncology was only used in the treatment of cancer, that had already spread but, now it can be used to start treatment in cases where the tumour is large or extending to the armpit.” Auvinen says.

Immuno-oncology, also, known as immunotherapy, helps the patient’s immune system to identify cancer cells and to attack them as enemies. “Immunotherapy can be targeted at immunologically active cancers. Of the different types of breast cancer, only triple negative breast cancer is immunologically active. In a best-case-scenario, neo-adjuvant treatment can eliminate breast cancer completely but, longer-term treatment outcomes are still being studied.”

Immunotherapy doesn’t necessarily cause any other side effects than fatigue. In some patients, however, it can make the immune system to attack healthy organs, possibly, leading to, for example, skin, liver or gastrointestinal inflammation, heart symptoms or diabetes even months after treatment.

“This is why immunotherapy requires good collaboration and communication with the patient. The patient’s family and other health care professionals, too, must understand the link between immunotherapy and various possible symptoms.”

In the treatment of hormone-dependent breast cancer, no similar innovations are on the horizon. However, genetic profiling of the tumour is a new opening in the planning of treatment. It can be used to get a more accurate assessment of the risk of cancer recurrence and, consequently, of the need for cytostatics, so that burdensome treatments are not initiated in vain.

When necessary, genetic profiling of the cancer tumour can, also, be used to select a suitable drug, if, for example, standard treatment chosen according to the biological cancer type doesn’t yield the desired results. “If cancer becomes resistant to treatment, an analysis of the genetic mutations of the tumour may provide insight into the type of drug that could be effective.” Says Professor Arto Mannermaa of the Institute of Clinical Medicine at the University of Eastern Finland.

In recent years, multi-professional Molecular Tumour Boards:MTB have been established in large hospitals to plan the treatment of individual patients, based on genetic profiling of their tumour. However, since genetic profiling is expensive, it is currently performed for a small number of patients only.

“At Kuopio University Hospital, the MTB began its work recently and it is, also, linked to the activities of FICAN East and the university’s multidisciplinary cancer research community. Genetic profiling can be purchased from commercial service providers abroad but, analytics can, also, be performed at the university, in which case researchers can be involved in interpreting the results and making their expertise, also, otherwise available to treatment planning.”

Cancer develops when mutations occur in the genome of cells, disrupting their normal function and causing them to divide uncontrollably. As tumour cells divide, they continue to mutate, which means that the multitude of genetic mutations may be different at different stages of cancer development and there, may, also, be internal variation in the tumour.

“The significance of mutations found in genetic tumour profiling and drugs, possibly, already found to be effective against them, can be studied in international, ever-expanding databases. However, data on all mutations is not readily available. Together with Professor Antti Poso’s research group, we will be exploring them with the help of computer modelling.” Mannermaa says.

Based in the School of Pharmacy at the University of Eastern Finland, the research group is capable of modelling the effects of a mutation and virtually testing all existing pharmaceutical ingredients for their effectiveness against that particular mutation. Poso, also, works as a visiting professor at the University of Tübingen in Germany, where this expertise is already being used to choose treatments for cancer patients in the university hospital.

“There are nearly 80,000 women in Finland, who have had breast cancer and in 20–30% of them, cancer will recur. We need a simple method for monitoring people, who have had breast cancer and for predicting cancer recurrence. Liquid biopsy could be a feasible tool and it is currently being studied extensively.” Mannermaa says.

In liquid biopsy, cancer biomarkers are searched in bodily fluids, such as, blood samples. Mannermaa’s research group has shown, e.g., that breast cancer patients with a poor prognosis can be identified, based on the degree of breakdown of circulating extracellular DNA released by the tumour.

An interesting finding was that this method could be used to identify patients with a poor prognosis from among patients with hormone-positive breast cancer, which is traditionally considered to have a good prognosis. In another study, the research group showed that breast cancer recurrence could be predicted by liquid biopsy from a blood sample months before the recurrence was detected during a medical examination. This was based on cancer mutations in extracellular DNA.

“Our next endeavour is to use liquid biopsy to isolate living, circulating cancer cells. Circulating cancer cells may play an important role in the formation of metastases. Analysing them may shed light on the progression of cancer. In the laboratory, the idea is to test pharmaceutical ingredients targeting the mutations they carry.”

In Finland, liquid biopsy is not yet routinely used but, according to Mannermaa, it, may, in the future supplement traditional methods in the diagnosis, prognosis assessment and monitoring of breast cancer, too.

Circulating biomarkers are, also, the topic of an on-going study examining how extracellular vesicles, i.e., messengers excreted into their surroundings by cancer cells, can promote resistance to treatment.

“Cells, that have been given radiation therapy seem to use vesicles to sound an alarm of a kind to other cells, possibly contributing to the development of resistance to treatment. We are now interested in how treatment changes the composition of vesicles, and what kind of cellular signalling pathways are affected.” :::ω:::

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Year Ninth: Day 02: Monday: September 25: 2023: The Humanion: We Are One











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