Drug for Skin Disease Boosts Hormone Treatment for Prostate Cancer

Clinical Trials

Immunotherapy Drug for Skin Disease Could Boost Hormone Treatment for Prostate Cancer

Wed, 06/27/2018 – 4:09pm by Institute of Cancer Research

A new form of immunotherapy reactivates the response to hormone treatment in advanced prostate cancer, a study in mice and human prostate cancer cells has found.

Hormone therapy is a mainstay of prostate cancer treatment – but tumour cells can grow resistant, leading to a hard-to-treat, advanced form of the disease.

The new study found that blocking a protein produced by a type of immune cell – known as granulocytic myeloid-derived suppressor cells – restored sensitivity to hormone therapy.

Drugs that block this protein, called IL-23, already exist and are used for autoimmune diseases such as the skin condition psoriasis.

Clinical trials are now planned to assess the possible benefit of this new form of immunotherapy alongside the next-generation hormone therapy enzalutamide, in men with advanced prostate cancer.

Scientists at The Institute of Cancer Research, London, worked with colleagues at the Institute of Oncology Research in Switzerland on the study, which was published in the prestigious journal Nature today (Wednesday).

The research was supported by funders including the Prostate Cancer Foundation in the US, Prostate Cancer UK, the Movember Foundation and Cancer Research UK.

The researchers studied mice, along with tumour and blood samples from prostate cancer patients treated at The Royal Marsden NHS Foundation Trust, to unpick the role of myeloid-derived suppressor cells in prostate cancer.

They found that blood and tumour samples from men with resistant prostate cancer contained higher levels of these suppressor immune cells and IL-23 than those from men whose cancer still responded to hormone therapy.

When they studied mice with prostate cancer that no longer produced IL-23, they found their tumours shrank considerably, and cancer cells grew more slowly.

It also took longer for the prostate tumours to become resistant to hormone therapy, and the mice survived for a longer period of time.

Both blocking IL-23 and stopping suppressor cells from moving into the tumour led to an improved response to hormone therapy, giving the researchers confidence that they identified a key mechanism that drives hormone therapy resistance in prostate cancer.

The researchers believe that IL-23 allows prostate cancer cells to sidestep the need for androgen hormones to fuel their growth.

Other immunotherapies, which work by reactivating the immune system’s ability to recognise and kill cancer cells, have shown some promise in prostate cancer, but only a subset of men respond well.

As myeloid-derived suppressor cells are present in many prostate tumours, the researchers believe that this immunotherapy approach could work in a large proportion of men with the disease.

Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“Hormone therapy works well in men with prostate cancer, but when cancer evolves to become resistant to treatment, other options are greatly reduced.

“Our study found an important interaction between hormone signalling and the immune system. We believe we could exploit this to reverse hormone resistance in prostate cancer, and boost the effect of widely used prostate cancer drugs such as enzalutamide.

“We are keen to start clinical trials to investigate how we can combine this new form of immunotherapy with existing hormone therapies, to improve treatment for men with advanced prostate cancer.”

Professor Andrea Alimonti, Professor of Oncology at the University of Italian Switzerland and Institute of Oncology Research (IOR), Bellinzona, Switzerland, said:

“When we discovered that IL23 producing-MDSCs were the main immune subset infiltrating prostate tumors that have acquired resistance to hormone-treatment, we immediately realised that these cells could be one of the cause behind the emergence of castration-resistant prostate cancer.

“This study describes a new unexpected mechanism by which the tumor immune response supports the growth of prostate cancer and it opens the way for future novel therapeutic applications for the treatment of metastatic prostate cancer patients.”

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

“Immunotherapies have shown great promise in many cancer types, but so far their benefit in prostate cancer has been limited to a small subset of men.

“This new study has uncovered a completely new way to modify the immune system to combat prostate cancer.

“A combination of hormone therapy with this new form of immunotherapy could be a really exciting new avenue of treatment for advanced prostate cancer, and it’s important this approach is tested in clinical trials.”

Howard Soule, Ph.D., executive vice president and chief science officer of the Prostate Cancer Foundation, said:

“This important study identifies an immune protein that enables resistance to anti-androgen therapy, and suggests that targeting this protein may be effective in the treatment of men with castrate-resistant prostate cancer.”

Caging Kidnapped Babies A Trial Run For Fascism

stolen from logo the irish times

Fintan O’Toole: Trial runs for fascism are in full flow

Babies in cages were no ‘mistake’ by Trump but test marketing for barbarism

Tue, Jun 26, 2018

To grasp what is going on in the world right now, we need to reflect on two things. One is that we are in a phase of trial runs. The other is that what is being trialled is fascism – a word that should be used carefully but not shirked when it is so clearly on the horizon. Forget “post-fascist” – what we are living with is pre-fascism.

It is easy to dismiss Donald Trump as an ignoramus, not least because he is. But he has an acute understanding of one thing: test marketing. He created himself in the gossip pages of the New York tabloids, where celebrity is manufactured by planting outrageous stories that you can later confirm or deny depending on how they go down. And he recreated himself in reality TV where the storylines can be adjusted according to the ratings. Put something out there, pull it back, adjust, go again.

Fascism doesn’t arise suddenly in an existing democracy. It is not easy to get people to give up their ideas of freedom and civility. You have to do trial runs that, if they are done well, serve two purposes. They get people used to something they may initially recoil from; and they allow you to refine and calibrate. This is what is happening now and we would be fools not to see it.

One of the basic tools of fascism is the rigging of elections – we’ve seen that trialled in the election of Trump, in the Brexit referendum and (less successfully) in the French presidential elections. Another is the generation of tribal identities, the division of society into mutually exclusive polarities. Fascism does not need a majority – it typically comes to power with about 40 per cent support and then uses control and intimidation to consolidate that power. So it doesn’t matter if most people hate you, as long as your 40 per cent is fanatically committed. That’s been tested out too. And fascism of course needs a propaganda machine so effective that it creates for its followers a universe of “alternative facts” impervious to unwanted realities. Again, the testing for this is very far advanced.

Moral boundaries

But when you’ve done all this, there is a crucial next step, usually the trickiest of all. You have to undermine moral boundaries, inure people to the acceptance of acts of extreme cruelty. Like hounds, people have to be blooded. They have to be given the taste for savagery. Fascism does this by building up the sense of threat from a despised out-group. This allows the members of that group to be dehumanised. Once that has been achieved, you can gradually up the ante, working through the stages from breaking windows to extermination.

It is this next step that is being test-marketed now. It is being done in Italy by the far-right leader and minister for the interior Matteo Salvini. How would it go down if we turn away boatloads of refugees? Let’s do a screening of the rough-cut of registering all the Roma and see what buttons the audience will press. And it has been trialled by Trump: let’s see how my fans feel about crying babies in cages. I wonder how it will go down with Rupert Murdoch.

To see, as most commentary has done, the deliberate traumatisation of migrant children as a “mistake” by Trump is culpable naivety. It is a trial run – and the trial has been a huge success. Trump’s claim last week that immigrants “infest” the US is a test-marketing of whether his fans are ready for the next step-up in language, which is of course “vermin”. And the generation of images of toddlers being dragged from their parents is a test of whether those words can be turned into sounds and pictures. It was always an experiment – it ended (but only in part) because the results were in.

‘Devious’ infants

And the results are quite satisfactory. There is good news on two fronts. First, Rupert Murdoch is happy with it – his Fox News mouthpieces outdid themselves in barbaric crassness: making animal noises at the mention of a Down syndrome child, describing crying children as actors. They went the whole swinish hog: even the brown babies are liars. Those sobs of anguish are typical of the manipulative behaviour of the strangers coming to infest us – should we not fear a race whose very infants can be so devious? Second, the hardcore fans loved it: 58 per cent of Republicans are in favour of this brutality. Trump’s overall approval ratings are up to 42.5 per cent.

This is greatly encouraging for the pre-fascist agenda. The blooding process has begun within the democratic world. The muscles that the propaganda machines need for defending the indefensible are being toned up. Millions and millions of Europeans and Americans are learning to think the unthinkable. So what if those black people drown in the sea? So what if those brown toddlers are scarred for life? They have already, in their minds, crossed the boundaries of morality. They are, like Macbeth, “yet but young in deed”. But the tests will be refined, the results analysed, the methods perfected, the messages sharpened. And then the deeds can follow.
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fintan otoole
Fintan O’Toole

Fintan O’Toole has been an op-ed columnist for the paper since 1988. His column on political and social affairs appears every Tuesday. He also writes for the Culture Shock slot on Saturdays. A former literary editor of The Irish Times, he has written more than a dozen books; most recently he edited the book of the newspaper’s series Modern Ireland in 100 Objects. Awards include the AT Cross Award for Supreme Contribution to Irish Journalism