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Reviewed by Emily Henderson, B.Sc. Mar 17 2023

Tyrosine kinase inhibitors are a type of targeted cancer medicine that can attack specific types of cancer cells and prevent them from multiplying. Although these inhibitors, called TKIs, can be very useful in fighting certain cancers, they also cause serious inflammatory side effects that limit their use. A Japanese research team has discovered the underlying mechanism that causes this inflammation. This study revealed the underlying mechanism by which the TKIs cause inflammation, and therefore provides the molecular basis that is essential to overcome the inflammatory-based side effects."

Atsushi Matsuzawa, Professor at the Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University

The team's findings were published in The Journal of Immunology on February 6, 2023.

These TKIs are essential anticancer drugs. However, the use of TKIs frequently initiates inflammation in the body, such as the lung disease interstitial pneumonitis. From their earlier studies, the team had learned that a representative TKI called Gefitinib (GF) causes lung inflammation. GF is a helpful cancer medication used in treating certain breast, lung, and other cancers. It works by targeting the epidermal growth factor receptors. When the GF is used to treat the cancer, it can also cause inflammation in the patient's lungs, through the NLRP3 inflammasome. The NLRP3 inflammasome is part of the body's immune system and plays an important role in innate immunity. But when the NLRP3 inflammasome is improperly activated, it can contribute to the development of a wide range of inflammatory diseases.

Until now, scientists have not fully understood why the NLRP3 inflammasome is activated, but the evidence seems to point to mitochondrial dysfunction. When mitochondria are healthy, they work like batteries, producing energy in the body's cells. Mitochondrial dysfunction happens when the mitochondria do not work as they should because of disease. In their earlier study, the team learned that the GF activated the NLRP3 inflammasome through mitochondrial damage that led to the interstitial pneumonitis in patients. However, they had not understood how GF initiates the mitochondrial damage and whether or not other TKIs also shared this mechanism. Cancer Research eBook Compilation of the top interviews, articles, and news in the last year. Download a free copy

To conduct their study, the team looked at the tyrosine kinases, those enzymes that work as a kind of "on" and "off" switch in many of the cells' functions. They specifically studied the Src family kinases, called SFKs. The SFKs are nonreceptor tyrosine kinases that regulate many cell processes. There are 11 types of SFKs in the human genome. Some of these SFKs are in the mitochondria and they play an essential role in the function of the mitochondria. The team found that all the TKIs they tested inhibit the kinase activity of the SKFs in the mitochondria which is responsible for the NLRP3 inflammasome.

The team's comprehensive analysis of the TKIs they tested revealed that these TKIs act as powerful agonists. In addition, the team observed off-target activity that could contribute to the side effects. "As an important finding, all TKIs we tested share a common off-target activity against the mitochondrial SFKs. Therefore, blocking the access of TKIs to mitochondria is a good way to prevent the inflammation," said Matsuzawa. They also noted that the other TKIs that do not affect the activity of the mitochondrial SFKs may overcome the inflammatory-based side effects. As another approach, when effective inhibitors of the NLRP3 inflammasome are developed, administering the TKIs at the same time as the NLRP3 inhibitors can counteract the side effects. The team's results provide insight into both the biological and the clinical significance of the NLRP3 inflammasome and the SFKs.

Looking ahead, the team's next step is to propose a new approach to avoid the inflammatory-based side effects of TKIs. They hope to lead in the development of new TKIs that do not initiate inflammation.

The research team includes Yuto Sekiguchi, Saya Takano, Takuya Noguchi, Tomohiro Kagi, Ryuto Komatsu, Maoko Tan, Yusuke Hirata, and Atsushi Matsuzawa from the Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan. Source:

Tohoku UniversityJournal reference:

Sekiguchi, Y., et al. (2023) The NLRP3 inflammasome works as a sensor for detecting hypoactivity of the mitochondrial Src family kinases. The Journal of Immunology. doi.org/10.4049/jimmunol.2200611.

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Energy bills: Network charges set to rise as price cap eases

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Energy bills: Network charges set to rise as price cap eases

A major component within household energy bills is set to rise sharply from next year to help pay for efforts to maintain energy security during the transition to green power.

The industry regulator Ofgem’s draft determination on how much it will allow network operators to charge energy suppliers from 1 April 2026 to 31 March 2031 would push up network costs within household bills by £24 a year.

These charges currently account for 22% of the total bill.

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The findings, which will be subject to consultation before a final determination by the end of the year, reflect demands on network operators to make power and gas networks fit for the future amid expansion in renewable and nuclear energy to meet net zero ambitions.

Ofgem says the plans it has given provisional approval for amount to a £24bn investment programme over the five-year term – a four-fold increase on current levels.

A total of 80 major projects includes upgrades to more than 2,700 miles of overhead power lines.

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If rubber stamped as planned, the resulting network cost increases threaten further upwards pressure on bills from next April – a month that has now become synonymous with rising essential bills.

The watchdog revealed its plans as the 22 million British households on the energy price cap benefit from the first decline for a year.

It is coming down from an annual average £1,849 between April and June to £1,720 from July to September.

That’s on the back of easing wholesale costs seen during the spring – before the temporary surge in wholesale gas prices caused by the recent instability in the Middle East.

A new forecast released by industry specialist Cornwall Insight suggested households were on track to see a further, but slight, decline when the cap is adjusted again in October.

At the current level it is 28% lower than at the height of the energy-led cost of living crisis – but 10% higher than the same period last year.

The price cap does not limit total bills because householders still pay for the amount of energy they consume.

Ofgem is continuing to recommend consumers shop around for fixed rate deals in the market as they can offer savings compared with the price cap and shield homes from any price shocks seen within their fixed terms.

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Jonathan Brearley, the regulator’s chief executive, said: ”Britain’s reliance on imported gas has left us at the mercy of volatile international gas prices which during the energy crisis would have caused bills to rise as high as £4,000 for an average household without government support.

“Even today the price cap can move up or down by hundreds of pounds with little we can do about it.

“This record investment will deliver a homegrown energy system that is better for Britain and better for customers. It will ensure the system has greater resilience against shocks from volatile gas prices we don’t control.

“These 80 projects are a long-term insurance policy against threats to Britain’s energy security and the instability of prices. By bringing online dozens of homegrown, renewable generation sites and modernising our energy system to the one we will need in the future we can boost growth and give ourselves more control over prices too.

“Doing nothing is not an option and will cost consumers more – this is critical national infrastructure. The sooner we build the network we need, and invest to strengthen our resilience, the lower the cost for bill payers will be in the future.”

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Trump’s Big Beautiful Bill in overtime as senators jam crypto clauses

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Trump’s Big Beautiful Bill in overtime as senators jam crypto clauses

Trump’s Big Beautiful Bill in overtime as senators jam crypto clauses

US senators are in a marathon vote-a-rama over amendments to Donald Trump’s massive tax and spending bill, with one lawmaker bidding to include tax cuts for crypto.

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Culture secretary Lisa Nandy hits out at BBC over Glastonbury controversy

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Criminal investigation launched into Glastonbury performances of Kneecap and Bob Vylan

The culture secretary has claimed there is “a problem of leadership” at the BBC, as the controversy over Bob Vylan’s Glastonbury performance deepens.

Lisa Nandy criticised the corporation over its decision not to pull the livestream after the band’s frontman shouted “death, death to the IDF” – referring to the Israel Defence Forces – on Saturday.

A criminal investigation has been launched into the Glastonbury performances of both Bob Vylan and Kneecap after the police reviewed footage.

Ms Nandy condemned the “appalling and unacceptable scenes” at Glastonbury and said the government would not tolerate antisemitism.

She said she had called BBC director-general Tim Davie after the broadcast of Bob Vylan’s set to find out why it had aired, and why the feed had not been cut.

“I expect answers to these questions without delay,” she said.

Culture Secretary Lisa Nandy leaves 10 Downing Street, London, following a Cabinet meeting. Picture date: Tuesday June 24, 2025.
Image:
Culture Secretary Lisa Nandy. Pic: PA


Later, when asked in the Commons about the BBC’s editorial processes and who would be held accountable, Ms Nandy replied: “When you have one editorial failure, it’s something that must be gripped. When you have several, it becomes a problem of leadership.”

Ms Nandy said she had spoken to members of the Jewish community, including attendees at Glastonbury, who said they were concerned by imagery and slogans and ended up creating their own “safe space”.

Mr Davie has been facing calls for his resignation.

Yesterday, drummer Bobbie Vylan released a video statement on Instagram – saying politicians who have spent time criticising the band should be “utterly ashamed” for giving “room” to this over other issues.

The punk rap duo have had their US visas revoked and been dropped by their US representative, United Talent Agency.

He also addressed what was said on stage, saying: “Regardless of how it was said, calling for an end to the slaughter of innocents is never wrong. To civilians of Israel, understand this anger is not directed at you, and don’t let your government persuade you that a call against an army is a call against the people.”

Shortly after it was posted, the video was no longer available to view.

Israel denies targeting civilians in its war in Gaza.

Moglai Bap and Mo Chara of Kneecap perform at Glastonbury. Pic: Reuters
Image:
Moglai Bap and Mo Chara of Kneecap perform at Glastonbury. Pic: Reuters

During Kneecap’s set, one member suggested on stage starting a “riot” outside his bandmate’s forthcoming court appearance, before clarifying he meant “support”.

In a statement, Avon and Somerset Police said that after reviewing footage of the performances of Kneecap and Bob Vylan, further enquiries are required and a criminal investigation is now being undertaken.

“A senior detective has been appointed to lead this investigation,” a spokesperson said. “This has been recorded as a public order incident at this time while our enquiries are at an early stage.”

The force said the investigation will be “evidence-led and will closely consider all appropriate legislation, including relating to hate crimes”.

“We have received a large amount of contact in relation to these events from people across the world and recognise the strength of public feeling,” it added. “There is absolutely no place in society for hate.”

Bob Vylan performing on the West Holts Stage, during the Glastonbury Festival at Worthy Farm in Somerset. Yui Mok/PA Wire
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Bob Vylan performing on the West Holts Stage. Pic: PA

What happened?

During Bob Vylan’s set, the duo performed in front of a screen that showed several messages, including one that said Israel’s actions in Gaza amount to “genocide”.

Bobby Vylan also led chants of “death to the IDF”.

The set was live streamed by the BBC as part of its Glastonbury coverage, but has not been made available on demand.

Politicians including the prime minister have criticised the performance. Glastonbury organiser Emily Eavis said the chants “crossed a line” and that there was no place at the festival for “antisemitism, hate speech or incitement to violence”.

A BBC spokesperson said the broadcaster respected freedom of expression “but stands firmly against incitement to violence”.

They added: “The antisemitic sentiments expressed by Bob Vylan were utterly unacceptable and have no place on our airwaves…

“The team were dealing with a live situation, but with hindsight we should have pulled the stream during the performance. We regret this did not happen.”

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What’s the Glastonbury controversy?

Media watchdog Ofcom said it was in talks with the BBC and that the broadcaster “clearly has questions to answer” over the stream.

Irish-language rap trio Kneecap were on stage afterwards. Before their appearance at the festival, there had been calls for Glastonbury to remove them from the bill – as rapper Liam Og O hAnnaidh (who performs as Mo Chara) is facing a terror charge, accused of displaying a flag in support of the proscribed group Hezbollah at a gig in London last November.

Glastonbury organisers kept them on the line-up, but the BBC chose not to stream their set live. An edited version was later made available on demand.

On stage, the band led chants of “f*** Keir Starmer”.

O hAnnaidh’s bandmate Naoise O Caireallain (Moglai Bap) said they would “start a riot outside the courts” for O hAnnaidh’s next appearance, before clarifying: “No riots, just love and support, and support for Palestine.”

Hundreds of people turned out in protest for his first court appearance earlier this month.

Read more:
Who are Bob Vylan?

Festival performers criticise political interference

Bob Vylan were set to perform in Chicago, Brooklyn and Philadelphia in the autumn. They are due to perform at Radar Festival in Manchester on Saturday and Boardmasters, a surfing and music festival in Newquay, Cornwall, in August.

Sharing a statement on Instagram after the Glastonbury set, Bobby Vylan said: “Teaching our children to speak up for the change they want and need is the only way that we make this world a better place.

“As we grow older and our fire starts to possibly dim under the suffocation of adult life and all its responsibilities, it is incredibly important that we encourage and inspire future generations to pick up the torch that was passed to us.”

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The war in Gaza started after Hamas militants launched attacks in Israel on 7 October 2023, killing 1,200 people and taking roughly 250 hostages.

More than 860 Israeli soldiers have been killed since the war began, more than 400 of them during the fighting in Gaza.

Israel’s offensive in Gaza has devastated the enclave and killed around 56,500 people, according to the Hamas-run health ministry, which does not differentiate between civilians and combatants, but says more than half of the dead are women and children.

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