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Thema: Presse: Glioblastom

Presse: Glioblastom
27.04.2021 08:34:18Neu
Eine israelische Wissenschaftlerin hat ein Protein entdeckt, dass für die Ausbreitung von maligen Gliomzellen im Gehirn verantwortlich ist. Ihr Ansatz ist dieses Protein zu blocken, um gegen Glioblastom vorzugehen.

In einer Studie an Mäusen und am menschlichen Gliomgewebe sind die Ergebnisse fantastisch. Alle behandelnden Mäuse haben das Gliom überlebt.

"But when SELP was inhibited, the tumor cells had a slower division rate, stopped migrating to the brain and were less invasive. The positive result (for the mice at least): the cancer’s progression in the brain was dramatically hindered."

"All the mice with tumors died within weeks. However, those given a chemical compound that blocks production of the SELP protein all recovered."

Kann es am Ende so einfach sein? In jedem Fall muss eine Phase 1 Studie so schnell wie möglich erfolgen. Tierversuche haben in der Vergangenheit immer wieder vielversprechende Ergebnisse geliefert, ohne das diese in späteren Studien wiederholt werden konnten.

Cure for deadly brain cancer may be on its way
Glioblastoma is an aggressive cancer that accounts for most malignant brain tumors. An Israeli researcher may have found its weak spot.

By Brian Blum April 14, 2021, 8:00 am

Glioblastoma is a particularly aggressive form of brain cancer, accounting for half of all primary brain cancers. It has a 40 percent survival rate after a year and just 5% after five years, even after surgery, radiation and chemotherapy.

Researchers at Tel Aviv University have discovered a potential treatment, tested on mice and 3D lab models so far.

If it works on humans, glioblastoma could become “chronic but manageable,” says Prof. Ronit Satchi-Fainaro, director of the university’s Cancer Biology Research Center and Cancer Research and Nanomedicine Laboratory. “It could even cure it completely.”

What Satchi-Fainaro and her team discovered is that glioblastoma results in part from a failure in the brain’s immune system, which leads to the amplification of cancerous cell division.

This immune system misstep is tied to the secretion of a protein called P-Selectin (SELP) which, when bound to the brain’s microglia immune cells, alters their function so that, rather than inhibiting the spread of cancer cells, they do the opposite.
Glioblastoma cells. Image courtesy of TAU

Since cells communicate with each other via proteins, the researchers investigated which proteins are secreted when the microglia encounter glioblastoma cells. They found that six proteins were overexpressed.

Satchi-Fainaro next blocked each of the six proteins in turn, to see if one in particular was the main culprit in blocking the brain’s immune function. It was SELP that was disrupting the immune system and boosting the tumors.

SELP normally helps cells – white blood cells in particular – travel inside the body. The problem is that “the encounter between glioblastoma cells and microglia cells causes them to express SELP in large quantities,” Satchi-Fainaro explains.

That allows the cancer cells to travel and penetrate the brain tissue. The tumor “corrupts and reeducates” the microglia so that instead of defending the brain against cancer, it generates more SELP.

But when SELP was inhibited, the tumor cells had a slower division rate, stopped migrating to the brain and were less invasive. The positive result (for the mice at least): the cancer’s progression in the brain was dramatically hindered.

Dramatic effects

For the study, Satchi-Fainaro and her team modified hundreds of mice to give them glioblastoma.

All the mice with tumors died within weeks. However, those given a chemical compound that blocks production of the SELP protein all recovered.

The same effect was found on tumor cells taken from human patients and inserted into a 3D model of the human brain in a lab.

ISRAEL21c profiled Satchi-Fainaro in our article on bio-convergence. where we looked at her work with 3D-printed tumors that allow cancer physicians to “try out” drugs on a perfect copy of the actual tumor.

While addressing brain cancer was Satchi-Fainaro’s main goal in her glioblastoma study, another benefit has been discovered: Inhibiting SELP can ease the pain associated with sickle cell anemia.

The next step is proving that inhibiting SELP is safe in humans. If so, Satchi-Fainaro hopes that approval of the treatment will be given quickly.

“Glioblastoma patients need new treatments immediately,” she says.

“Glioblastoma is the deadliest type of cancer in the central nervous system, accounting for most malignant brain tumors. It is aggressive, invasive, and fast-growing, making it resistant to existing treatments, with patients dying within a year of the cancer’s onset. Moreover, glioblastoma is defined as a ‘cold tumor’, which means that it does not respond to immunotherapeutic attempts to activate the immune system against it.”

She adds: “Our treatment may be the needed breakthrough in the battle against the most daunting cancer of all. It is paving the way for a new therapy for a disease that hasn’t had anything new in terms of treatment over the last decade.”

The study, published in the journal Nature Communications, was led by PhD student Eilam Yeini in collaboration with neurosurgeons from Tel Aviv Sourasky Medical Center, who supplied glioblastoma tissue samples removed during surgery. Neurosurgeons from Johns Hopkins University and the Lieber Institute in the United States supplied healthy brain tissue from autopsies.

Satchi-Fainaro recently won the Youdim, Bruno, Humboldt and Kadar Family Awards for outstanding research in 2020.

Her groundbreaking study was funded by the Israel Cancer Research Fund, the European Research Council, the Morris Kahn Foundation, the Israel Cancer Association and the Israel Science Foundation.
27.04.2021 14:22:03Neu
Crizanlizumab, ein Antikörper gegen P-Selektin ist im Herbst 2020 von der EMA zugelassen worden, allerdigns für eine andere Anwendung, zur Behandulg von Sichelzellkrankheit.

04.05.2021 13:58:04Neu
Hallo Rawa,
ich habe Herrn Eilam Yeini angeschrieben und ihn gefragt, was er von der Idee mit Crizanlizumab hält. Er antwortete mit heute Folgendes:

Our research that was published in Nature Communications focused on preclinical studies testing the inhibitor on glioblastoma cells in 3D human cultures (brain tumor spheroid models) and on animal models. Unfortunately, at the moment, Crizanlizumab, as well as other SELP inhibitors, were not tested on glioblastoma patients and are approved for human trials at this point. Thus, we do not know their safety or efficacy on patients with advanced brain tumors. We hope that our findings will be translated into a new treatment for glioma patients in the future.

Leider recht zurückhaltend, aber irgendwie habe ich dennoch Hoffnung, dass sich hier mehr ergibt.

Liebe Grüße
04.05.2021 16:02:13Neu
Hallo Katzenmama,

ich finde es toll dass du EIlam Yeini angeschrieben hast.

Seine Antwort ist für mich wenig überaschend, er kennt das Medikament wohl nicht, es hat auch erst kürzlich eine Zulassung erhalten.

Ich werde auch die Neurologin von meinem Vater darauf ansprechen beim nächsten Termin. Laut Beipackzettel ist mit diesen Nebenwirkungen zu rechnen:

Die große Frage ist, können die Resultate am Menschen wiederholt werden.
04.05.2021 16:06:01Neu
Ich finde den Ansatz interessant, warum verbreitet sich der Glioblastom überhaupt? Es ist mal was anderes als den Tumor mit immer anderen Kombinationen von Zytostatika zu bekämpfen die mal besser mal schlechter wirken.
04.05.2021 16:54:40Neu
Hallo rawa,
ich habe die E-Mail von Herrn Ellam Yeini so verstanden, dass das Medikament Crizanlizumab ihm zwar ist, es aber nicht erforscht ist bei Patienten mit Glioblastomen. Herr Yeini hat noch auf die folgende kürzlich veröffentliche Studie hingewiesen:


Ich habe gelesen, dass dies auch schon in diesem Forum geschrieben wurde. Daher habe ich das nicht noch zusätzlich erwähnt.
04.05.2021 17:17:44Neu
Mich hat es verunsichert, dass er diese für ihn fremde Studie vielversprechender (?) als seine eigene hält. Ich hoffe irgendwie trotzdem auf diesen neuartigen Ansatz. Melde mich, sobald ich mehr weiß.
04.05.2021 17:18:41Neu
Hallo Katzenmama,

Das kenne ich, 2 von 10 Patienten haben einen positiven Verlauf gehabt, ein Patient hat 22 Monate später keinen Anzeichen mehr vom Tumor beim anderen ist der Tumor gesumpft, über die anderen 8 wird nicht berichtet. Ernüchternd, dass er auf diese Studie verweist