Combination of two cancer drugs make pancreatic tumors treatable with immunotherapy methods (Repurposed lung fibrosis drug makes other drug(s) kill cancer cells)

Medical Xpress / Technical University Munich / Nature Cancer ^ | Feb. 4, 2022 | Chiara Falcomatà et al

[ConservativeMind]

Pancreatic carcinoma is a tumor with an extremely poor prognosis for which effective treatments have not yet been found. A team has now discovered a way of making pancreatic tumors treatable with immunotherapy methods using a targeted combination of two cancer drugs. The researchers believe that the promising combined approach could also prove effective with other cancer types.

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. The disease is almost always fatal, with a 10-year survival rate of around 1 percent. The prognosis is especially poor for a subgroup of these tumors known as mesenchymal PDAC subtype.

The drug trametinib showed early promise with cancers that activate the RAF-MEK-ERK signaling pathway. Because pancreatic cancers of the mesenchymal subtype show the highest activation of this pathway, it appeared likely that a drug that inhibits this pathway could offer therapeutic benefits. Experiments showed, however, that treatments with trametinib alone were insufficient.

The researchers conducted high-throughput screening of 418 drugs to find whether one of them would improve the therapeutic effect of trametinib. They discovered that nintedanib, a drug already approved for lung fibrosis treatment, stimulated T-cells infiltration when used in combination with trametinib. "The combination of the two drugs led to cell cycle arrest and the death of cancerous cells. They also changed the microenvironment of the tumor," says Dieter Saur, explaining the underlying mechanism.

Next the researchers investigated whether these changes could sensitize mesenchymal pancreatic carcinomes for treatment with immune checkpoint inhibitors. "The responses we observed in mice showed us that the anti-PD-L1 immunotherapy improved the effect of the combination treatment with trametinib and nintedanib," says Chiara Falcomatà, the first author of the study. "The triple treatment significantly improved the response of the tumor, leading to a clear survival advantage of the highly aggressive mesenchymal PDAC subtype."

[ConservativeMind]

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[Lurker]

Thanks. A friend of ours currently has Stage 4 Pancreatic cancer. I’m going to forward this.

L

[ConservativeMind]

Give these, too:

Team discovers that a derivative of vitamin B3 prevents liver cancer in mice

The inverse relationship between NAD+ and cancer awakened the curiosity of the researchers: could an increase in NAD+ have beneficial effects on the disease? When the scientists supplemented the diet in genetically modified mice with nicotinamide riboside, a derivative of vitamin B3 that increases intracellular levels of NAD+, they did not observe tumour development. Surprisingly, when they gave this diet to mice that had already developed the disease, the size of the tumours was reduced and they eventually disappeared.

The results have been reproduced in other types of cancer such as pancreatic cancer. “We observed the same results in mice with pancreatic adenocarcinoma with regards to DNA damage, so we could conclude that this treatment is effective on tumours caused by oncogene-induced DNA damage and thus, deficit in NAD+,” says Krishna Tummala, first author of the study.

https://medicalxpress.com/news/2014-11-team-derivative-vitamin-b3-liver.html

Also:

Reprogramming the Tumor Stroma: A New Paradigm (Vitamin D helps reverse pancreatic cancer stroma (biofilm/scar tissue)):
https://www.cell.com/cancer-cell/fulltext/S1535-6108(14)00379-1

Plant extract shows promise in treating pancreatic cancer
https://www.sciencedaily.com/releases/2016/02/160211184014.htm

Traditional Herbal Medicine Kills Pancreatic Cancer Cells, Researchers Report (Black seed oil)
https://www.sciencedaily.com/releases/2008/05/080519092215.htm

Celery, artichokes contain flavonoids that kill human pancreatic cancer cells
https://www.sciencedaily.com/releases/2013/08/130815172358.htm

Lycopene Inhibits Reactive Oxygen Species-Mediated NF-κB Signaling and Induces Apoptosis in Pancreatic Cancer Cells
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6521322/

[libh8er]

The cold reality is successful outcomes in mice means nothing for humans. Lots of successful experiments on mice have failed miserably in human trials. Secondly immunotherapy for pancreatic cancers has fared poorly because it’s hard for the T cells to penetrate the tumor microenvironment. How are they going to get around that ? Maybe they have found a way.

[silverleaf]

Fabulous news

[aimhigh]

and in ten years, this treatment might see the light of day.

[shotgun]

And the media will give the credit to Joe Biden for his cancer moonshot program.

[ConservativeMind]

The true cold reality is that sure short-term death is upon them with no chance of change, so anything relatively harmless, with some positive proof behind it, is useful.

For that matter, look at post #4’s studies and simple things to try.

[Honorary Serb]

.....Secondly immunotherapy for pancreatic cancers has fared poorly because it’s hard for the T cells to penetrate the tumor microenvironment.....

Well, that’s part of what they’re trying to overcome.

Nevertheless, it’s still only in mice, albeit with a transplanted human tumor.

[Fish Speaker]

If this works out, you’ll only get it if your E/S/G score is high enough ...

[lurk]

Bless you all who are involved with pancreatic adenocarcinoma. My wife succumbed a month ago.

Adenocarcinoma is the undefeated beast so far, and treatments only have a small effect on select genetic groups or early diagnosis, which is rare due to its invisibility.

The Israelis have the most hopeful treatment theory going, with the discovery of a protein that the cancer cell ingests at the moment of division. Keep an eye on it.

[libh8er]

I am not trying to put a damper on these experiments. All experiments, successful and less successful, lead to increase in the sum total of human knowledge which ultimately increases the chances of success down the road. The path to success is paved with failure. That has been the story of human innovation for centuries. People only remember the successes but not the failures that led to success. Look at all of Elon Musk’s failures for example until reusable rocket technology was perfected. It’s possible the human trials for the new therapy will turn out just as well as in mice, but until human trial results are out we should exercise a little caution. That’s all I meant.

[wita]

Sorry for your loss.

[JusPasenThru]

Effective therapy for pancreatic cancer is like Hillary! being arrested. I’ll believe it when I see it.

[entropy12]

My wife was diagnosed with stage-4 cancer 4 years ago. Chemi
, Radiation and Keytruda has helped her fight cancer and stay alive. She was able to do several cruises since diagnosis, next cruise sails on Monday. The cancer treatments are amazing.

[Robert357]

bump for reference