Ferroptosis Article (NIH)

[Hoosier Investor]

Here's a good (long) article discussing the topic of ferroptosis in neurological diseases. "Emerging Mechanisms and Targeted Therapy of Ferroptosis in Neurological Diseases and Neuro-oncology"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274504/

I've only scanned the article, but it appears in some cases it's good to induce ferroptosis while in other cases it's good to inhibit ferroptosis. I welcome additional thoughts of those with a better understanding of the science / topic.

Shown below is an excerpt from the article....
"Sorafenib, sulfasalazine, and artesunate are some of the clinical drugs approved by the U.S. Food and Drug Administration (FDA) that can induce ferroptosis in many cancer types. Clinically, there is an urgent need for drugs that induce new ferroptosis for the treatment of tumors."

[Hoosier Investor]

Reposting the ferroptosis (in cancer) article put forward by Bigfun....

https://www.ncbi.nlm.nih.gov/pmc/articl ... 0of%20GPX4

[Hoosier Investor]

I still need to read through the articles, but I believe my prior comment is likely incorrect in that I'm not sure it would ever be desirable to inhibit ferroptosis as part of a treatment. Instead, I believe some chemo drugs also inhibit ferroptosis when administered. This inhibition of ferroptosis undermines the chemo drug's effectiveness. Thus, if you can supplement the chemo treatment with a separate drug that induces ferroptosis, then the combination treatment can be more effective than treatment via the chemo drug alone.

If Imetelstat can induce ferroptosis, then perhaps it could serve as the second drug in a combination (chemo) treatment.

[Bigfun]

Hi Hoosier, thanks for your thoughts and setting up this thread. I was reading through the other article you posted and was really interested in the other diseases where ferroptosis may play a role. There is a lot to think about there. There are many terms that I will need to lookup just to try and get a perspective on this.

At least it is clear though that there is an opportunity for synergy with other compounds that would be complimentary to a ferroptosis inducing agent. The way I picture it is that ferroptosis will crack open the door and let all that good poison in to do it's work on the cancer cells. Easier said than done though, I am sure.

Combing through it again I found this statement to be interesting regarding immunotherapy. The idea of a "vaccine-like effect" sounds a little bit like what the MAIA folks have mentioned when talking about the effect of their drug. I would wonder if Imet has ever been tested with an immunotherapy agent? Maybe something else to try in combos.

"There are two approaches to reversing immunotherapy resistance by inducing ferroptosis: a tumor cell-intrinsic approach that induces ferroptosis in cancer cells to elicit a vaccination-like effect to stimulate antitumor immunity and a tumor cell-extrinsic approach that triggers ferroptosis in the TME to deplete immune suppressor cells."

Also found this info on MD Anderson site. More high level but also talks about how radiation therapy induces ferroptosis. I always had a much more simplistic idea that it "just burned things away".

https://www.mdanderson.org/cancerwise/w ... on%2Dgamma.

[LWS]

Previous from Sat Dec 30, 2023

Imetelstat for Diseases other than Cancer

With the discussion of Ferroptosis comes the discussion of Imetelstat for diseases other than cancer. This will be of interest to potential partners and collaborators.

1/ Ferroptosis (Inflammation in a variety of diseases)
2/ Telomerase & Telomeres
3/ Combinations
4/ Synergies
5/ Oral form potential
=======================

What is the link between Inflammation and Cancer? (from MD Anderson)

Myth: Inflammation is one condition.
Truth: The term inflammation actually refers to many different processes in the body.

“When the medical community talks about inflammation, we aren’t just talking about one thing, one organ or even the same type of inflammation,” Watowich says.

Inflammation is a local or systematic reaction from the cells in our immune system, but research has shown that there are different types of inflammation and that cells from other parts of the body are also involved. For example, the cells that line our blood vessels and the cells that line our skin also have inflammatory responses, so we know that it’s a more broad reaction that can involve cells throughout the body.


Myth: Inflammation is bad.
Truth: “Inflammation has a bad rap,” Watowich says. “But the truth is that we couldn’t live without it.”

But inflammation isn’t strictly good or bad. It can be either, depending on how long the inflammation lasts. Small flare-ups of inflammation are good since it’s our immune system working to heal our bodies, but chronic inflammation can be a sign of something more concerning such as rheumatoid arthritis, type 2 diabetes or even cancer.

“I encourage cancer patients to think of inflammation broadly,” Watowich says. “We have to understand inflammation in its context to understand if it’s helping or hurting.”


Myth: Inflammation always causes cancer.
Truth: Inflammation can contribute to the development of certain cancers. For example, Watowich cites the tight association of chronic inflammatory bowel diseases, such as ulcerative colitis or Crohn’s disease, and the development of colorectal cancer. But she adds that the connection hasn’t been established with other cancers and may not even exist. However, inflammation has been linked to the spread of cancer to other parts of the body.

At the same time, there are types of inflammation that help kill tumors. For example, immunotherapies can capitalize on inflammatory processes to attack and treat cancer.


Inflammation’s tie to immunotherapy

MD Anderson’s Center for Inflammation and Cancer is working to better understand cancer’s relationship with inflammation, ranging from how inflammation is involved in tumor growth to how inflammation can help fight cancer.
===================
Note: Dr. Stephanie Watowich is Professor and Deputy Chair in the Department of Immunology and the Director of the Center for Inflammation and Cancer at MD Anderson Cancer Center.