By Michael Greenwood, M.Sc. Reviewed by Danielle Ellis, B.Sc.
Enzymes in cancer diagnosis
Enzymes in cancer therapy
References
Further reading
Enzymes are proteins that facilitate biochemical reactions by acting as a catalyst, and thus, their expression and activity have a strong influence on the reactions taking place within cells. As enzymes are involved at every stage of cell regulation, a better understanding of their role and function allows them to be exploited in the clinic, both as diagnostic and therapeutic agents.
Image Credit: Design_Cells/Shutterstock.com Enzymes in cancer diagnosis
Metabolic changes within cells are a hallmark of cancer, where genetic aberrations reduce or enhance the generation of enzymes and their metabolic products. This has allowed enzymes to be utilized as cancer biomarkers, providing a diagnostic and prognostic marker that clinicians may use to characterize a tumor.
Enzymes were among the first biomolecules utilized as cancer biomarkers, with the serine protease prostate-specific antigen (PSA) identified as a prognostic tool for prostate cancer in the 1980s. PSA is produced by the secretory cells that line the prostate glands and eventually reach the sera. Higher PSA in the blood is a result of greater numbers of more densely packed cells in the prostate, indicative of malignant cancer.
Similarly, numerous enzyme-related biomarkers for ovarian cancer have also been identified, such as the downregulation of apolipoprotein A1 and the downregulation and truncation of transthyretin.
The protein products of enzyme interactions can also be used in cancer diagnosis in the study of the proteome. The proteome consists of a large number of low and ultra-low molecular-weight protein fragments and is a rich source of information regarding the state of the cell. The proportion of specific low-molecular-weight proteins in a cell can be used to infer the activity and number of enzymes, which might otherwise be hard to distinguish from the many other proteins in the cell.
Enzymes are additionally useful in biomolecule identification and cancer diagnosis as an analytical tool in the form of the enzyme-linked immunosorbent assay (ELISA). ELISA can indicate the bonding of a target molecule colorimetrically or fluorimetrically, exploiting the highly specific binding of enzymes. Enzymes in cancer therapy
Besides their use in cancer diagnosis, enzymes are also involved in cancer therapy, both as targets of therapeutic methods and as a therapeutic tool. For example, where an abundance of enzymes induced by dysregulated genetic transcription is causing the cancer cell to proliferate more quickly, drugs can be used to target and thus regulate the population of this enzyme, slowing the spread of cancer. Alternatively, where the absence of a particular enzyme is encouraging cancer-like behavior, introducing therapeutic enzymes can help control the proliferation of a tumor. Related StoriesMetabolic syndrome linked to higher pancreatic cancer risk, study showsNew drug combo shows promise in targeting RAS-mutant multiple myelomaNew study challenges "gold standard" opioid treatment for cancer pain
Administration of pro-enzymes trypsinogen and chymotrypsinogen A have demonstrated potent anti-tumor effects against a range of cell lines while limiting angiogenesis, growth, and migration. It is thought that the primary influence of these pro-enzymes is to encourage the breakdown of filamentous protein structures that grow quickly to supply the tumor with blood. Enzymes have also been used to enhance the effect of other therapeutic efforts. For example, uridine diphospho-glucuronosyltransferase (UGT) enzymes are found in the cytosol and are involved in the glucuronidation reaction, often used to remove cellular pollutants from the cytosol.
In various cancer states, upregulation of UGT is observed, which can limit the function of the anti-cancer drug irinotecan. UGT enzyme inhibitor drugs (vorinostat) have been applied to patients exhibiting high levels of UGT enzymes, demonstrating a return of efficacy of chemotherapy.
The manipulation of metabolic pathways by the inhibition of enzymes is the goal of numerous therapeutic strategies. One pathway of particular interest to cancer treatment is the management of reactive oxygen species (ROS). ROS are essential to multiple cell signaling pathways, but high concentrations of ROS can be damaging to surrounding biomolecules and induce genetic mutation and apoptosis.
Poor blood flow and acidic conditions within tumors promote the generation of ROS, and many chemo- and radiotherapeutic approaches directly induce the generation of ROS in both target and non-target cells, causing the death of cancer cells but also severe side effects. Cellular antioxidant and ROS-generating enzymes can also be damaged by the cancer therapy applied or the resulting increase in ROS concentration, further destabilizing the dynamics of ROS control within cells.
The Monoamine oxidase A (MAO-A) enzyme is involved in ROS regulation and is commonly up or downregulated in tumors. High expression of the MAO-A has been associated with poor clinical outcomes in prostate cancer patients, associated with excessive ROS concentrations. Drug inhibition of MAO-A has been found to eliminate tumor growth and metastasis in some mouse models, limiting the spread of cancer by modulating ROS generation. References Liang and Chan (2007) Enzymes and Related Proteins as Cancer Biomarkers: a Proteomic Approach. Clin Chim Acta.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104743/ Wu and Qu (2012) Cancer Biomarker Detection: Recent Achievements and Challenges. RSC.
https://pubs.rsc.org/en/content/getauthorversionpdf/c4cs00370e Peran et al. (2017) A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer. Scientific reports.
https://www.nature.com/articles/s41598-017-14571-x Pathania et al. (2018) Drug metabolizing enzymes and their inhibitors' role in cancer resistance. Biomedicine & pharmacotherapy.
https://www.sciencedirect.com/science/article/pii/S0753332218317050 Liu et al. (2018) Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer. Oncology letters.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778774/
Further ReadingAll Cancer ContentWhat is Cancer?What Causes Cancer?Cancer GlossaryCancer ClassificationMore…
Stephen Graham says the rise of “misogynistic tendencies” is concerning and we’re “all accountable to an extent” to finding a solution.
His new limited series Adolescence looks at the impact of social media on children and the accessibility to radicalised views online.
Speaking to Sky News, Graham says there was a certain moment for him that inspired him to create the show.
Image: Stephen Graham as Eddie Miller in Adolescence. Pic: Netflix
“I read an article about a young girl who was stabbed to death by a young boy, and then a few months later, on the news there was a young girl who, again, had been brutally stabbed to death by a young boy in a completely different part of the country.
“If I’m really honest with you, that hurt my heart and I just thought, why? Why does this kind of thing happen? What is this society? Why have we reached this point where this kind of thing is happening? What was the reason?”
The four-part drama, he says, doesn’t have the answer but instead holds a mirror up to society asking how can the growing presence of incel culture be quashed?
“You look at it and you see that we’re kind of all accountable to an extent. There’s failings within the school system, there’s situations where the education system can look at this, look at what’s happened with that kind of rise in these misogynistic tendencies.
More on Stephen Graham
Related Topics:
“The society as a whole can look at this, parents obviously can look at this, and the government in many ways.”
What is the term incel?
Derived from the phrase “involuntarily celibate”, an incel culture in its simplest is someone who deems themselves unable to find a romantic partner despite desiring one.
A more radicalised sub-culture of incels has surfaced online in recent years which includes individuals who dislike feminism and believe that women have become too sexually selective.
They believe men are the superior sex and men have the right to objectify and criticise women as a result.
Influencers like Andrew Tate have been connected to the growing corner of the internet in which young boys are being radicalised from the certain viewpoint.
Image: Ashley Walters as Detective Inspector Bascombe in Adolescence. Pic: Netflix
Actor Ashley Walters, who stars alongside Graham in the series, says reading into the existence of the misogynistic group came as a bit of a shock and it worries him about the world children are growing up in.
“I’d seen bits of the Andrew Tate stuff kind of popping up online or whatever, but I never really delved into it. And for me, this was the first real experience.
He adds: “I do sometimes feel sorry for [kids]. When I was growing up, I was in a bubble. I didn’t have a clue what was going on in the States and other parts of the world.
“It was just kind of in my little area that I grew up in with my family… I wasn’t seeing Bentleys and designer clothes and all of this stuff. It’s like I was happy with what I had. And now you’re exposed to everything. It’s no wonder that kids mentally grow up quicker.”
The Top Boy actor believes it can be hard for young boys to talk about their emotions.
“It’s really important that we have these conversations and we make it normal to have discussions just like women and young girls do about feelings and whatever they’re going through.
“That was one of the big reasons why I wanted to be a part of this conversation that we’re creating, because I’m a strong advocate for, as a man, being vulnerable, crying in front of my friends, and just saying how I feel.
“It’s even difficult for me at times, so I can’t imagine how young men are at the moment… everything that’s going on around social media in their lives, how difficult it is for them to start this conversation.”
‘This government needs to do something’
Co-creator and writer Jack Thorne agrees and says the government should step in and guide children and their parents to the correct use of social media.
“I think this government needs to do something. And there’s a private members’ bill going through the Commons on Friday that has been watered down quite extensively by this government because they’re frightened of big tech.
“And we need to be having conversations like Australia’s having conversations, whether they’re actually putting in legislation about restricting social media access.
“We need to be having those conversations in this country and we’re not. And if we don’t have these conversations, it is going to get worse.”
Image: Fatima Bojang as Jade in Adolescence. Pic: Netflix
He adds: “Doing this show I spent a lot of time in a lot of dark places. I saw where the web went and where the web goes. And it’s not about Andrew Tate. Andrew Tate is the shorthand for adults.
“There’s much worse stuff out there. And it teaches kids a logic… that makes sense of the world for them in a really distorted and ugly way. And unless we look at that and talk about that, things are only going to get worse.”
A government spokesperson said: “We are committed to keeping young people safe online.
“Starting next week, Ofcom can begin enforcing the Online Safety Act’s illegal content duties, targeting the most harmful material.
“By summer, children will be protected from harmful content, and platforms must take steps to ensure age-appropriate experiences online.
“These protections will act as the foundation and our priority is implementing them quickly and effectively.
“We also know there will be more to do and have already acted, including commissioning a study to assess current research on the impact of social media and smartphones, strengthening the evidence base on their impact on children’s wellbeing.
“This will enable us to swiftly consider all options to inform our next steps in the safety of children online.”
Reform UK’s most senior woman has told Sky News the Rupert Lowe row “doesn’t look great” and she doesn’t “want to see it in the news any more days”.Â
Dame Andrea Jenkyns, who defected to Reform last year, accepted it was “clearly a big falling out” but suggested these spats do not always cut through to the public.
She insisted she was concentrating on winning as she looks to become the party’s first ever mayor in May.
In an interview with Sky News, Dame Andrea also spoke for the first time about her experience of domestic abuse, denying Reform has a “woman problem” but accepted “we need to start talking more about issues, what women are interested in”.
Having lost her seat as a Conservative in the 2024 election, Dame Andrea briefly quit politics only to return earlier this year as Reform’s newest recruit.
She is now standing as the party’s candidate to become the first Greater Lincolnshire mayor, in a race that psephologists think could be Reform’s best hope of turning itself from a party of protest into one that is governing.
That’s because Reform is on the march in Lincolnshire, which is a key battleground between the Conservatives and Reform in the local and mayoral elections in May.
More on Lincolnshire
Related Topics:
Richard Tice, Reform’s deputy leader, took the Conservative seat of Boston and Skegness in the last election as Reform came second in a further two of the county’s eight constituencies.
Image: Dame Andrea spoke to Sky News’ Beth Rigby
This farming country has long been part of the patchwork of Conservative England and it is in these heartlands that Reform hopes it can land a significant blow to its political rivals in the coming weeks.
“It’s a worry,” admits one Labour insider who doesn’t much relish the prospect of having to deal with a newly minted Reform party mayor should Dame Andrea win in May against Labour candidate Jason Stockwood, the Conservative Rob Waltham and independent Marianne Overton.
There is also the Lincolnshire council race, which Reform is targeting. All 70 seats are up for grabs and the Conservatives, which have a 38-seat majority, are defending 53 seats. The only way is up for Reform here, while the Conservatives, who have held this council for 10 of the past 13 elections, are bracing for a drubbing.
Tories say Jenkyns is from Yorkshire
The Conservatives make the point that they have a “strong local candidate who is born and bred in Lincolnshire, whereas Dame Andrea is from Yorkshire” when I ask them about the race.
“We are fighting hard, we have a proven track record of delivery in charge of local services whereas Reform aren’t tried and tested,” the Conservatives said.
“And if they’re anything like Reform nationally, who don’t turn up on important votes, then they won’t show up for people locally.”
Dame Andrea is still based in Yorkshire where she used to be an MP, as this is where her son attends school. But she rents a place in Lincolnshire and has vowed to move to the county should she win the mayoralty.
She also points out that she grew up in Lincolnshire and was a local councillor before moving to Yorkshire after her shock victory over Ed Balls in the 2015 general election.
Image: Dame Andrea is hoping to become Reform’s first mayor
‘Fed up’ farmers eyeing Reform
When we meet her on the road in Lincolnshire, she takes us to meet some farmers whose livelihoods are under intense pressure – be it over local flooding and flood defences or changes to inheritance tax and farming subsidies that are affecting their farms.
There is little love for Labour in the gathering of farmers, who in the main seem to be lapsed Conservative voters that are now eyeing Reform, as a number of them tell me how they are fed up with how the Environment Agency and local politicians are running their area.
“We’re fed up with all of them,” said one farmer.
“We just want some action. As farmers we know drainage is so important, we just want to get it sorted.”
They are also alarmed and anxious about the inheritance tax changes introduced by Labour and are pressing for carve-outs for small farms handed down from generation to generation amid fears they will have to sell up to pay the inheritance tax bills.
But the troubles at the top of Reform hadn’t gone unnoticed by this group. Unprompted, one of the farmers raised the row between the suspended Reform MP Rupert Lowe and the party leadership, telling Dame Andrea that while he “really likes Reform” he doesn’t much like what he’s seeing at the moment.
Please use Chrome browser for a more accessible video player
1:25
Reform UK row explained
‘Spat looks worse because Reform is small’
The farmer said: “I don’t follow politics avidly. But I just look and say [Rupert Lowe] is full of common sense and I really like him and I don’t know what’s happened, but it looks from outside [he has been] chucked under the bus.
“And I’m like, am I getting second thoughts about Reform? I don’t know what’s gone on, but it concerns me about what’s going on with Reform.”
Dame Andrea tries to downplay it and says the “spat” looks worse because it’s a smaller party.
“To me it’s about the movement, the right policies, to carry on. What is the alternative? This will blow over and Reform will keep getting strong,” she said.
Can Jenkyns and Farage co-exist?
Dame Andrea would clearly like the infighting to stop, but it raises questions for me about how she will fit into this very male-dominated party, in which all four MPs are male, with Dame Andrea the only senior woman beyond the former Conservative minister Ann Widdicombe.
She is, like Nigel Farage, a disrupter – Dame Andrea was one of the first Tories to call for Theresa May and Rishi Sunak to stand down, and a conviction politician who fervently backed Boris Johnson and Brexit.
If she does win this mayoral race she will be a big personality in Reform alongside Farage, which leaves me wondering if they can co-exist in a party already at war.
Image: Dame Andrea says she doesn’t think the party has a ‘woman problem’
Jenkyns was in an abusive relationship
Reform does struggle with female voters, with fewer women voting for the party against all age cohorts, young to old. Dame Andrea tells me she doesn’t think the party has a “woman problem”, but she does think it needs to talk about more issues that she thinks women are interested in, citing education, special educational needs and mental health.
When I raise the matter of violence against women and how the party has handled revelations that one of its own MPs was jailed in a youth detention centre as a teenager for assaulting his girlfriend, Dame Andrea reveals to me she has been in an abusive relationship.
“I know how it can break you. I know how you sort of start losing your identity. So I’ve been on that side,” she said.
“And I’ve also helped constituents to fight against this, so it matters, we need to do more in society because whether it’s men or women, one is too much in my view.”
Spreaker
This content is provided by Spreaker, which may be using cookies and other technologies.
To show you this content, we need your permission to use cookies.
You can use the buttons below to amend your preferences to enable Spreaker cookies or to allow those cookies just once.
You can change your settings at any time via the Privacy Options.
Unfortunately we have been unable to verify if you have consented to Spreaker cookies.
To view this content you can use the button below to allow Spreaker cookies for this session only.
Out on the campaign trail, even in the Labour territory of Lincoln where Hamish Falconer is the local MP, Dame Andrea gets a warm welcome. She tells me she thinks she can win it: “I might be living in blind hope here. But I’ve got that feeling.”
This corner of England has become a test bed for Reform to see if it can turn from a party of protest into one that has a shot at governing in the form of a regional mayor.
If Reform can succeed in that – what might come next? It would be a remarkable comeback for Dame Andrea and a remarkable victory for Reform too.
Ministers have been priming Labour MPs and the public for cuts to a ballooning welfare bill since the start of the year.
Image: Baroness Harriet Harman said people criticising Liz Kendall should ‘shut up’
Asked what she thought of briefings against Ms Kendall as welfare cuts loom, Baroness Harman said: “I hate those sorts of briefings.
“I don’t think anybody should be briefing against Labour ministers who are trying to implement the manifesto.
“You know, she is incredibly competent and leads a really dedicated team. So I think they should just shut up and pull together.”
More on Benefits
Related Topics:
Image: Work and Pensions Secretary Liz Kendall. Pic: PA
More and more Labour MPs have publicly criticised the impending benefit cuts, with many concerned they will hit people with disabilities the most.
Downing Street has taken the unusual step of calling all 404 Labour MPs into Number 10 over Wednesday and Thursday for briefings on the changes ahead of the details being released next week.
Baroness Harman said she thinks Ms Kendall is a “rising star” and is “absolutely certain” the PM and chancellor will stand behind her.
The peer was social security secretary – the equivalent of Ms Kendall’s job now – at the start of Tony Blair’s first term after Labour’s 1997 landslide win.
Please use Chrome browser for a more accessible video player
0:52
‘Government’s plan to cut welfare is terrifying’
She was forced to defend benefit cuts just after they came to power and said there are “lots of parallels between what we were trying to do then, and what the government is trying to do now”.
However, she said the difference is, in 1997 she was making the argument for welfare cuts to help single parents into work by herself, but Ms Kendall is being backed by Rachel Reeves and Sir Keir Starmer.