New potential cancer treatment

[Dave]

SCIENTISTS in Scotland have found a way to trigger the death of cancer cells that they believe could be more effective than current methods.

The new method – Caspase Independent Cell Death (CICD) – led to the complete eradication of tumours in experimental models. Currently, most anti-cancer therapies (chemotherapy, radiation and immunotherapy) work through a process called apoptosis, which activates proteins known as caspases, leading to cell death.

However in apoptosis, therapies often fail to kill all cancer cells, leading to disease recurrence and can have unwanted side effects that may even promote cancer. Now, the Scots scientists believe they may have found a way to improve therapy while pre--venting unwanted toxicity.

http://www.express.co.uk/news/uk/846889/Glasgow-cancer-experts-kill-tumours-breakthrough

[hermes2015]

Fantastic news. I hope it does not take too long to get approval for use in patients.

[xSilverPhinx]

Very interesting!

[Recusant]

This sort of item pops up now and then. Possible ways of beating the wretched disease that's taken so many. Not to get hopes up too high, but people are still working on it.

"How this cancer drug could make radiation a slam dunk therapy" | EurekAlert

Radiation is one of the most effective ways to kill a tumor. But these therapies are indiscriminate, and they can damage healthy tissues.

Now, UC San Francisco scientists have developed a way to deliver radiation just to cancerous cells. The therapy combines a drug to mark the cancer cells for destruction and a radioactive antibody to kill them. 

It wiped out bladder and lung tumors in mice without causing lethargy or weight loss – the typical side effects of radiation therapy.

"This is a one-two punch," said Charly Craik, PhD, a professor of pharmaceutical chemistry at UCSF and co-senior author of the study, which appears Dec. 10 in Cancer Research. "We could potentially kill the tumors before they can develop resistance." 

[Continues . . .]

The paper is open access:

"Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C-MHC I complex Demonstrates the Antitumor Efficacy of Hapten-Based Strategies" | Cancer Research

Abstract:

Antibody-based therapies have emerged as a powerful strategy for the management of diverse cancers. Unfortunately, tumor-specific antigens remain challenging to identify and target. Recent work established that inhibitor-modified peptide adducts derived from KRAS G12C are competent for antigen presentation via MHC I and can be targeted by antibody-based therapeutics, offering a means to directly target an intracellular oncoprotein at the cell surface with combination therapies.

Here, we validated antigen display of "haptenated" KRAS G12C peptide fragments on tumors in mouse models treated with the FDA-approved KRAS G12C covalent inhibitor Sotorasib using PET/CT imaging of an 89Zr-labeled P1B7 IgG antibody, which selectively binds Sotorasib-modified KRAS G12C MHC I complexes. Targeting this peptide-MHC I complex with radioligand therapy using 225Ac- or 177Lu-P1B7 IgG effectively inhibited tumor growth in combination with Sotorasib.Elucidation of the 3.1 Å cryo-EM structure of P1B7 bound to a haptenated KRAS G12C peptide-MHC I complex confirmed that the Sotorasib-modified KRAS G12C peptide is presented via a canonical binding pose and showed that P1B7 binds the complex in a T-cell receptor-like manner.

Together, these findings demonstrate the potential value of targeting unique oncoprotein-derived, haptenated MHC I complexes with radioligand therapeutics and provide a structural framework for developing next generation antibodies.

[The Magic Pudding..]

It wiped out bladder and lung tumors in mice without causing lethargy or weight loss – the typical side effects of radiation therapy.
[Continues . . .]

Obviously we can't apply a mouse model directly to us but there are a lot of mouse breakthroughs happening.
How long until we achieve infinite mouse? and could hyper-intelligent pan-dimensional beings be involved?

[zorkan]

Science is doing its best, but I'm not sure it will ever be able to eliminate all cancers.
Meanwhile.
"Maintain A Healthy Weight.
Exercise Regularly.*
Don't Smoke Or Use Smokeless Tobacco.
Eat a Healthy Diet.
Limit Alcohol – Zero Is Best.
Protect Yourself from the Sun And Avoid Tanning Beds.
Protect Yourself From Sexually Transmitted Infections.
Get Screening Tests."

My advice is don't think the more you exercise the healthier you will become.

[Recusant]

It wiped out bladder and lung tumors in mice without causing lethargy or weight loss – the typical side effects of radiation therapy.
[Continues . . .]

Obviously we can't apply a mouse model directly to us but there are a lot of mouse breakthroughs happening.
How long until we achieve infinite mouse? and could hyper-intelligent pan-dimensional beings be involved?

When we have mice that live for a couple of decades then things could get more interesting. Sometimes the mouse breakthroughs eventually arrive for at least some of us so more power to them. Though I doubt they'd consent to the endeavor if asked. Leaving the pan-dimensional folks to those who enjoy spinning tall tales.

[Recusant]

I came across the item below and immediately thought of this thread, the last few posts in particular. 

Essentially, an anti-cancer treatment that appears effective in mice doesn't produce similar results in humans because of a trait that evolved in rodents millions of years ago. Doesn't yet suggest supermice, but does expose a significant limitation in using a mouse model to develop particular cancer treatments.

'Scientists unveil surprising human vs mouse differences in a major cancer immunotherapy target' | EurekAlert!

Since its discovery in the 1990s, "programmed cell death protein 1," or PD-1, has been regarded as a leading target in cancer treatments. A "checkpoint" receptor that often resides on the surface of immune system cells, the PD-1 molecule works as a type of off switch that keeps immune cells from attacking other cells.

After its discovery, which revolutionized oncology and earned a 2018 Nobel Prize, researchers developed new drugs to block PD-1 and unleash the body's immune system to fight cancer. Yet treatments leveraging PD-1 are only effective in a small fraction of cancer patients, highlighting the need for a deeper understanding of how PD-1 works. Much of our current knowledge of PD-1's functions comes from studies in mice, grounded on the assumption that rodent and human biology operate similarly.

Researchers in UC San Diego's School of Biological Sciences and School of Medicine have now discovered that this assumption may be flawed. In a comprehensive assessment of PD-1 that featured novel biochemical analyses, animal modeling and a new evolutionary roadmap tracing PD-1 back millions of years, the UC San Diego scientists and their colleagues at the Chinese Academy of Sciences found that PD-1 in mice is significantly weaker than the human version.

The study, led by assistant project scientist Takeya Masubuchi, revealed several previously unknown PD-1 characteristics, including a "motif" — a specific sequence of amino acids — that is vastly different in rodents and humans.

"Our work uncovers unexpected species-specific features of PD-1 with implications for developing better pre-clinical models for PD-1," said Associate Professor Enfu Hui of the School of Biological Sciences, Department of Cell and Developmental Biology, and a senior author of the paper. "We found a motif in PD-1 that's present in most mammals, including humans, but is surprisingly missing in rodents, making rodent PD-1 uniquely weaker."

Continues . . .

The paper is behind a paywall.

Editor's summary:

Preclinical studies in mice have been critical to understanding how the inhibitory receptor PD-1 functions. However, human and murine PD-1 share less than 60% amino acid identity.

Masubuchi et al. found that human PD-1 was more inhibitory compared with murine PD-1 because of stronger binding interactions with its ligands PD-L1 and PD-L2 and more effective recruitment of the Shp2 phosphatase. A motif highly conserved across PD-1 orthologs in vertebrates but absent from rodents promoted Shp2 interactions.

Evolutionary analyses suggest that ancient rodents lost this motif in PD-1 after a major extinction event. Humanization of this motif or the intracellular domain of PD-1 reduced tumor-specific T cell responses in mice. These findings define key distinctions of rodent and human PD-1 orthologs.

[Recusant]

Progress in making life better for mice continues . . .

Seriously though, having known a few people who were taken out by leukemia, it's good to hear that a new treatment may be coming.

"A common diabetes drug may prevent leukemia, mouse study suggests" | Medical Xpress

Metformin, a widely used and affordable diabetes drug, could prevent a form of acute myeloid leukemia in people at high risk of the disease, a study in mice has suggested. Further research in clinical trials will be needed to confirm this works for patients.

The results of the study are published in Nature.

Around 3,100 people are diagnosed with acute myeloid leukemia (AML) each year in the UK. It is an aggressive form of blood cancer that is very difficult to treat. Thanks to recent advances, individuals at high risk of AML can be identified years in advance using blood tests and blood DNA analysis, but there's no suitable treatment that can prevent them from developing the disease.

In this study, Professor George Vassiliou and colleagues at the University of Cambridge investigated how to prevent abnormal blood stem cells with genetic changes from progressing to become AML. The work focused on the most common genetic change, which affects a gene called DNMT3A and is responsible for starting 10–15% of AML cases.

[Continues . . .]

[Dark Lightning]

That's good news, if it works. I have an elevated risk for acute myeloid leukemia due to having a "precursor" condition. Odds are 25% that I could contract this or multiple myeloma. It's stable for now, fortunately, though I am anemic.

[Tank]

I take that for diabetes 3 limes a day.

[Dark Lightning]

It works for diabetes, I get that. I meant if it actully works on those blood disorder issues.

[Tank]

Understood. I was just making and anecdotal observation.

[Dark Lightning]