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/
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Energy bills are to rise again next year, according to a respected forecaster.
Costs from January to March are projected to rise another 1% to £1,736 a year for the average user, according to research firm Cornwall Insight.
The energy price cap, which sets a limit on how much companies can charge per unit of electricity, is also expected to rise, costing typical households an extra £19 a year.
After the latest hike, there were hopes of a fall in the new year, but volatile wholesale gas and electricity markets are still above historic average costs.
Prices have gone up due to supply concerns arising from Russia‘s war in Ukraine, and maintenance of Norwegian gas infrastructure.
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But spring is expected to herald a reduction as is October 2025, Cornwall Insight said.
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‘Energy prices make me depressed’, pensioner Roy Roots said in August
Every three months energy regulator Ofgem revises the cap based on wholesale costs.
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The official January price cap announcement will be made on Friday.
It comes as millions of pensioners lost their automatic winter fuel allowance payment after the government means-tested the benefit.
Meanwhile, Cornwall Insight’s principal consultant Dr Craig Lowrey warned “millions” of households won’t heat their homes to “recommended temperatures, risking serious health consequences” with bills on the rise.
“With it being widely accepted that high prices are here to stay, we need to see action,” he said, suggesting options like cheaper rates for low-income homes, benefit restructuring, or other targeted support for the vulnerable “must be seriously considered”.
The energy price cap system is being reviewed by Ofgem with possible changes to the standing charge coming over the next year.
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Masked burglars have stolen farm vehicles from the Windsor Castle estate while members of the Royal Family are believed to have been asleep nearby.
Two men scaled a 6ft fence on the night of 13 October and used a stolen truck to break through a security gate, The Sun first reported.
The pair then fled with a pick-up and a quad bike that were stored in a barn.
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But the Prince and Princess of Wales, along with their three children George, 11, Charlotte, nine, and six-year-old Louis were believed to have been in their home, Adelaide Cottage, on the estate, according to The Sun.
The family moved there in 2022.
In a statement, Thames Valley Police said: “At around 11.45pm on Sunday 13 October, we received a report of burglary at a property on Crown Estate land near to the A308 in Windsor.
“Offenders entered a farm building and made off with a black Isuzu pick-up and a red quad bike. They then made off towards the Old Windsor/Datchet area.
“No arrests have been made at this stage and an investigation is ongoing.”
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The UK is braced for “disruptive snow” as yellow weather warnings cover large parts of the country until Tuesday – with the Met Office saying there is the “potential” for the alerts to be “escalated”.
The forecaster has warned up to 20cm of snow may accumulate in the worst affected areas as the country experiences its “first taste of winter”.
The Met Office has also told people to expect ice, cold temperatures and wintry showers this week.
A yellow warning for snow and ice is in place for much of the north of the country – covering areas in the East Midlands, Yorkshire, Wales and the north of England – from 7pm on Monday night to 10am on Tuesday morning.
Those in the impacted areas have been told power cuts are possible and mobile phone coverage might be affected.
The Met Office has said there is a “slight chance” some rural communities could be cut off and that bus and train services may be delayed or cancelled.
People are also warned to be careful not to slip or fall on icy surfaces.
The Met Office has said there will be bright spells across northern and eastern areas throughout today, but rain in the south and west will gradually spread northeastwards and turn to snow over northern hills.
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Tom Morgan, Met Office meteorologist, said: “We could see some disruptive snow in the Pennine regions, in particular, the Peak District as well, especially Monday night, but we could well see some impacts lasting on until Tuesday morning’s rush hour.
“Even down to lower levels, we could well see some snow as well, so quite a bit of disruption possible by Tuesday morning, and then the week ahead is likely to stay cold nationwide, a windy day on Tuesday, and then winter showers through the week ahead.”
Mr Morgan said that despite a “mild” start to the month, the cold conditions are more typical of “mid-winter to late-winter”.
“What we can say is that it’s going to be very cold for the time of year, there will be widespread overnight frosts, and a few locations where there’s snow on the ground,” he continued.
Meanwhile, a yellow snow and ice weather warning that came into force at 4pm on Sunday will end at 11am this morning.
The warning covers the northern tip of Scotland and people there have been told there may be icy patches on some untreated roads, pavements and cycle paths.
The Met Office has said there is “potential” for both yellow warnings to be “escalated”.
In southern England, a typical maximum temperature for this time of year is 11C (52F), but daytime highs for the week ahead are forecast to be around 5C (41F), while some parts of Scotland will reach “only just above freezing”, Mr Morgan said.
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The meteorologist said the public can best prepare for the wintry weather by checking their cars are suitable for icy and potentially snowy conditions and to take extra supplies including food, blankets and a fully charged mobile phone with them on journeys.
He added there were “likely” to be changes to the weather warnings in the coming days, and that “winter flurries” could be seen in the south of England later in the week.
Despite the cold conditions, the “whole of the UK” will enjoy more sunshine this week, the meteorologist added.
He said: “There’ll be some snow showers in the peripheries of the UK, particularly northern Scotland, and down the east and the west coast, but if you live inland and you live in the south, there’ll be lots of sparkly blue skies on the most days through Tuesday to Friday.”
It comes as a cold weather alert issued by the UK Health Security Agency, which was introduced at 9am on Sunday, will be in place until 9am on Thursday.
It covers a large area of England, north of Northhampton. The alert is triggered when there is a risk that healthcare services might face extra pressure and is designed to prepare those who are “particularly vulnerable” and “likely to struggle to cope”.