̽��ֱ�� of Cambridge - ovarian cancer

Cambridge Festival Speaker Spotlight: Dr Mireia Crispin

zs332 — Wed, 12 Feb 2025 14:03:02 +0000

Dr Mireia Crispin is an Assistant Professor in the Department of Oncology at the ̽��ֱ�� of Cambridge and leads a research group focusing on the development of multi-omic data integration models to understand how tumours evolve and respond to treatment.

Cancer isn’t fair – but care should be

lw355 — Sun, 04 Feb 2024 07:50:57 +0000

Listening to people's lived experiences is helping to improve the awareness and uptake of cancer care. On World Cancer Day, we take a look at some of the ways researchers are working with communities to ‘close the cancer care gap’.

Faulty BRCA genes linked to prostate and pancreatic cancers

cjb250 — Tue, 25 Jan 2022 21:00:40 +0000

A study published today in the Journal of Clinical Oncology has provided the strongest evidence to date of these links and helped researchers estimate more accurately the associated risk.

Since these genes were discovered in the mid 90s, numerous studies have explored possible links between BRCA1 and BRCA2 mutations and other cancers. However, these studies had small sample sizes, resulting in imprecise estimates of cancer risk. Being able to estimate the risks accurately is important for informing cancer prevention and screening strategies and providing genetic counselling to those at greatest risk. BRCA mutations are uncommon, affecting around 1 in 300-400 people in the population.

To further investigate these risk estimates, a team led by researchers at the ̽��ֱ�� of Cambridge, funded by Cancer Research UK, analysed data from almost 3,200 families with one or more members with the BRCA1 mutation and almost 2,200 families with members carrying the BRCA2 mutation. ̽��ֱ��families had all been recruited to the Consortium of Investigators of Modiﬁers of BRCA1/2. ̽��ֱ��researchers examined the associations with 22 primary cancers.

From the data, the researchers estimated that men who carry a BRCA2 mutation have a 27% risk of developing prostate cancer by the time they are 80 years old, more than double the rate compared to non-carriers. BRCA1 mutations were not associated with an increase in prostate cancer risk.

Carrying a defective copy of either BRCA1 or BRCA2 more than doubled an individual’s risk of pancreatic cancer to 2.5-3% by age 80.

̽��ֱ��mutations were also found to increase the risk of stomach cancer, though the researchers caution that because of the rarity of this form of cancer, the number of patients in their datasets was small.

Mutations in both genes significantly increased the risk of breast cancer in men, though the disease is still very rare, accounting for less than 1% of all male cancer cases in the UK. While a BRCA1 mutation increased a man’s risk of developing breast cancer more than four-fold to 0.4% by age 80, a BRCA2 mutation increased this risk by 44 times to 3.8% by age 80. It is estimated that 38 out of 1,000 male carriers of the BRCA2 mutation will develop breast cancer by age 80.

̽��ֱ��researchers were unable to find compelling evidence that mutations were linked to increased risk of some other cancers which were previously thought to be linked to faulty BRCA genes, such as melanoma.

Cancer Research UK says that people who are worried about their risk of cancer should talk to their GP. GPs can refer patients to a genetics clinic if they think someone has a strong family history and might be at an increased risk.

Professor Antonis Antoniou from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge, who led the research, said: “These large datasets of patients have allowed us to estimate with much greater accuracy the extent to which faulty BRCA1 and BRCA2 genes increase the risk of several cancers. We’ve known for some time that they’re linked to breast and ovarian cancer, but there’s been uncertainty about other cancers.”

Professor Marc Tischkowitz from the Department of Medical Genetics at the ̽��ֱ�� of Cambridge added: “ ̽��ֱ��link between BRCA2 and prostate cancer and pancreatic cancer is now much clearer, thanks to the data we’ve analysed. We have also identified a potential link with stomach cancer, but this is based on small numbers and needs further study. Our data suggests that there is no strong link between BRCA2 and melanoma, which may provide greater clarity to BRCA2 gene carriers.

“Overall, the results will add to our knowledge on optimising cancer screening and early detection strategies for people who are known to carry these faulty genes.”

Michelle Mitchell, Chief Executive of Cancer Research UK, said: “Our scientists helped to discover BRCA over 25 years ago and established that faults in these genes increase breast cancer risk. This study has built on that vital knowledge, giving us some important new insights into BRCA genes and the likely risks of developing prostate and pancreatic cancer.

“Cancers caused by inherited faulty BRCA genes are relatively rare, and other factors like age, smoking, diet and other preventable factors contribute to a person’s risk.

“Improving our understanding of how faults in our genes are associated with certain cancers puts us in a much better position to pinpoint those at a higher risk of developing cancer.”

Reference
Li, S et al. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants. Journal of Clinical Oncology; 25 Jan 2022; DOI: 10.1200/JCO.21.02112

Faulty versions of the BRCA1 and BRCA2 genes are well known to increase the risk of breast cancer in men and women, and in ovarian cancer. Now BRCA1 and BRCA2 have been linked to several other cancers, including those that affect men.

These large datasets of patients have allowed us to estimate with much greater accuracy the extent to which faulty BRCA1 and BRCA2 genes increase the risk of several cancers

Antonis Antoniou

KATERYNA KON/SCIENCE PHOTO LIBRARY

Prostate cancer cells

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‘Virtual biopsies’ could replace tissue biopsies in future thanks to technique developed by Cambridge scientists

cjb250 — Wed, 06 Jan 2021 09:47:55 +0000

̽��ֱ��research published in European Radiology shows that combining computed tomography (CT) scans with ultrasound images creates a visual guide for doctors to ensure they sample the full complexity of a tumour with fewer targeted biopsies.

Capturing the patchwork of different types of cancer cell within a tumour – known as tumour heterogeneity – is critical for selecting the best treatment because genetically-different cells may respond differently to treatment.

Most cancer patients undergo one or several biopsies to confirm diagnosis and plan their treatment. But because this is an invasive clinical procedure, there is an urgent need to reduce the number of biopsies taken and to make sure biopsies accurately sample the genetically-different cells in the tumour, particularly for ovarian cancer patients.

High grade serous ovarian (HGSO) cancer, the most common type of ovarian cancer, is referred to as a ‘silent killer’ because early symptoms can be difficult to pick up. By the time the cancer is diagnosed, it is often at an advanced stage, and survival rates have not changed much over the last 20 years.

But late diagnosis isn’t the only problem. HGSO tumours tend to have a high level of tumour heterogeneity and patients with more genetically-different patches of cancer cells tend to have a poorer response to treatment.

Professor Evis Sala from the Department of Radiology, co-lead CRUK Cambridge Centre Advanced Cancer Imaging Programme, leads a multi-disciplinary team of radiologists, physicists, oncologists and computational scientists using innovative computing techniques to reveal tumour heterogeneity from standard medical images. This new study, led by Professor Sala, involved a small group of patients with advanced ovarian cancer who were due to have ultrasound-guided biopsies prior to starting chemotherapy.

For the study, the patients first had a standard-of-care CT scan. A CT scanner uses x-rays and computing to create a 3D image of the tumour from multiple image ‘slices’ through the body.

̽��ֱ��researchers then used a process called radiomics – using high-powered computing methods to analyse and extract additional information from the data-rich images created by the CT scanner – to identify and map distinct areas and features of the tumour. ̽��ֱ��tumour map was then superimposed on the ultrasound image of the tumour and the combined image used to guide the biopsy procedure.

By taking targeted biopsies using this method, the research team reported that the diversity of cancer cells within the tumour was successfully captured.

Co-first author Dr Lucian Beer, from the Department of Radiology and CRUK Cambridge Centre Ovarian Cancer Programme, said of the results: “Our study is a step forward to non-invasively unravel tumour heterogeneity by using standard-of-care CT-based radiomic tumour habitats for ultrasound-guided targeted biopsies.”

Co-first author Paula Martin-Gonzalez, from the Cancer Research UK Cambridge Institute and CRUK Cambridge Centre Ovarian Cancer Programme, added: “We will now be applying this method in a larger clinical study.”

Professor Sala said: “This study provides an important milestone towards precision tissue sampling. We are truly pushing the boundaries in translating cutting edge research to routine clinical care.”

Fiona Barve (56) is a science teacher who lives near Cambridge. She was diagnosed with ovarian cancer in 2017 after visiting her doctor with abdominal pain. She was diagnosed with stage 4 ovarian cancer and immediately underwent surgery and a course of chemotherapy. Since March 2019 she has been cancer free and is now back to teaching three days a week.

“I was diagnosed at a late stage and I was fortunate my surgery, which I received within four weeks of being diagnosed, and chemotherapy worked for me. I feel lucky to be around,” said Barve.

“When you are first undergoing the diagnosis of cancer, you feel as if you are on a conveyor belt, every part of the journey being extremely stressful. This new enhanced technique will reduce the need for several procedures and allow patients more time to adjust to their circumstances. It will enable more accurate diagnosis with less invasion of the body and mind. This can only be seen as positive progress.”

This feasibility study, involving researchers from the Department of Radiology, CRUK Cambridge Institute, Addenbrooke’s Hospital, Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, and collaborators at Canon, was facilitated through the CRUK Cambridge Centre Integrated Cancer Medicine programme.

̽��ֱ��goal of Integrated Cancer Medicine is to revolutionise cancer treatment using complex data integration. Combining and integrating patient data from multiple sources – blood tests, biopsies, medical imaging, and genetic tests – can inform and predict the best treatment decisions for each individual patient.

̽��ֱ��study was funded by Cancer Research UK and ̽��ֱ��Mark Foundation for Cancer Research.

Reference
Lucian Beer, Paula Martin-Gonzalez et al. Ultrasound-guided targeted biopsies of distinct CT based radiomic tumour habitats: proof of concept. European Radiology; 14 Dec 2020; DOI: 10.1007/s00330-020-07560-8

A new advanced computing technique using routine medical scans to enable doctors to take fewer, more accurate tumour biopsies, has been developed by cancer researchers at the ̽��ֱ�� of Cambridge. This is an important step towards precision tissue sampling for cancer patients to help select the best treatment. In future the technique could even replace clinical biopsies with ‘virtual biopsies’, sparing patients invasive procedures.

This study provides an important milestone towards precision tissue sampling. We are truly pushing the boundaries in translating cutting edge research to routine clinical care

Evis Sala

Image showing individual and combined scans

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Family history and location of genetic fault affect risk for carriers of key breast and ovarian cancer genes

cjb250 — Tue, 20 Jun 2017 15:00:31 +0000

Cancer is caused by a combination of inherited genetic faults and environmental factors. While many hundreds of genetic mutations each increase an individual’s risk by a small amount, faults in two particular genes – BRCA1 and BRCA2 – are known to greatly elevate the risk of breast and ovarian cancers.

̽��ֱ��clinical management of women with faults in the BRCA1 and BRCA2 genes requires accurate estimates of their risk of developing breast cancer and how this changes with age. These can be used to estimate how prevention strategies such as medication, surgery and changing lifestyle factors reduce a woman’s risk, and can assist with decisions about the age to commence cancer screening, hence enabling better-informed decision-making.

Almost all previous reports on cancer risks for BRCA1 and BRCA2 mutation carriers have been based on ‘retrospective’ studies – looking at women who had already developed cancer – and estimates are therefore susceptible to biases associated with such study designs, for example inaccuracies in family history reporting and assessment in women born many decades previously (when breast cancer incidence was much lower) that are not relevant to today’s women.

Prospective cohort studies, in which scientists recruit and follow over time carriers of the mutations who have not yet developed breast cancer, overcome these issues. But the prospective studies of women with the BRCA1 and BRCA2 genes published to date have been very small, with the largest based on just 64 incident breast cancers.

Now, in a study published in JAMA: ̽��ֱ��Journal of the American Medical Association, an international team of researchers led by the ̽��ֱ�� of Cambridge, UK, has recruited almost 10,000 mutation carriers for a prospective cohort study. This enabled the team to estimate more precisely the breast and ovarian cancer risks for women with faults in BRCA1 and BRCA2.

“We have been able to provide the most precise estimates of age-specific risks to date,” says the study’s lead author, Dr Antonis Antoniou from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge. “These should provide more confidence in the counselling and clinical management of women with faults in the BRCA1 and BRCA2 genes.”

̽��ֱ��researchers found that 72% of women carrying a faulty BRCA1 gene will develop breast cancer risk and 44% will develop ovarian cancer by age 80. Similarly, they found that 69% of women carrying a faulty BRCA2 gene will develop breast cancer and 17% will develop ovarian cancer by age 80. However, for both cancers, a woman’s family history affected the risk – in other words, if a woman’s relative had had a breast cancer diagnosis, then her own risk would be higher than that of a carrier with no family history.

̽��ֱ��researchers also found that the position of the specific fault within the gene affected the cancer risk. Mutations in genes occur when the ‘letters’ of DNA – A, C, G and T – get ‘mistyped’ and replaced with a different letter.

“ ̽��ֱ��results show clearly and for the first time in a prospective study, that the cancer risks for women with faults in BRCA1 and BRCA2 depend both on the precise mutation and the woman’s family cancer history,” says Professor Douglas Easton, also from Cambridge and principal investigator of the UK-based EMBRACE study, the largest national cohort of women with mutations that contributed to the study.

Advances in sequencing technologies have opened up the potential of screening all women for BRCA1 and BRCA2 mutations, rather than just those with a significant family history of cancer, as is currently the case in the UK and most other countries. Such population-based screening, however, depends on having reliable estimates of risk to provide to women with and without a family history.

“Now that we understand more clearly the risks faced by women who carry these genetic faults, we should be in a better position to counsel them about the outcomes from screening and prevention programmes,” says Professor Gareth Evans, Consultant in Medical Genetics and co-author from ̽��ֱ�� of Manchester.

“This will also have practical implications on clinical management decisions, for example on the timing of surgery in order to reduce cancer risk. Such decisions tend to be taken around childbearing age, but some women with lower risks may opt to delay surgery until they complete their families.”

̽��ֱ��cancer risk estimates obtained by the present study were made possible because of over two decades of investment from Cancer Research UK, the European Union and other funders in establishing and following the cohorts.

Professor Arnie Purushotham, Cancer Research UK’s senior clinical adviser, said: “Women who carry faulty BRCA genes are much more likely to develop breast or ovarian cancers, and this large study could help women and their doctors better understand their risk of developing these cancers.

“This information – combining family medical history and the specific position of the faults in the BRCA genes – could help women decide the steps that they may want to take to reduce their risk of breast cancer, such as preventative surgery, medication or lifestyle changes.”

Reference
Kuchenbaecker, KB et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA; 20 June 2017; DOI: 10.1001/jama.2017.7112

A large scale study of women carrying faults in important cancer genes should enable doctors to provide better advice and counselling for treatments and lifestyle changes aimed at reducing this risk.

̽��ֱ��results show clearly... that the cancer risks for women with faults in BRCA1 and BRCA2 depend both on the precise mutation and the woman’s family cancer history

Doug Easton

MIKI Yoshihito

DNA

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Major genetic study identifies 12 new genetic variants for ovarian cancer

cjb250 — Mon, 27 Mar 2017 15:00:19 +0000

Published today in the journal Nature Genetics, the findings are the result of work by the OncoArray Consortium, a huge endeavour led by scientists in the UK, the USA and Australia. This particular study involved 418 researchers from almost 300 different departments worldwide.

According to Cancer Research UK, there were 7,378 new cases of ovarian cancer in the UK in 2014. Around nine out of ten of these cases was epithelial ovarian cancer. ̽��ֱ��peak rate of cases is among women aged 75-79 years old.

“We know that a woman’s genetic make-up accounts for about one third of her risk of developing ovarian cancer. This is the inherited component of disease risk,” explains Professor Paul Pharoah from the ̽��ֱ�� of Cambridge, UK, one of the joint leads. “We’re less certain of environmental factors that increase our risk, but we do know that several factors reduce the risk of ovarian cancer, including taking the oral contraceptive pill, having your tubes tied and having children.”

Inherited faults in genes such as BRCA1 and BRCA2 account for about 40 per cent of the inherited component. These faults are rare in the population (carried by about one in 300 people) and are associated with high lifetime risks of ovarian cancer – about 50 per cent for BRCA1 and 16 per cent for BRCA2 on average – as well as a high risk of breast cancer. Variants that are common in the population (carried by more than one in 100 people) are believed to account for most of the rest of the inherited component of risk.

Before the OncoArray Consortium, researchers had identified 27 common variants across the genome associated with ovarian cancer risk. However, some of these are associated only with rare subtypes of ovarian cancer. ̽��ֱ��magnitude of the associated risk however is modest: together, the variants account for only about 4 per cent of the inherited component of disease.

̽��ֱ��OncoArray Consortium studied the genomes of over 25,000 people with epithelial ovarian cancer and compared them to almost 41,000 healthy controls. They then analysed results from a further 31,000 BRCA1 and BRCA2 mutation carriers, which included almost 4,000 epithelial ovarian cancer patients. This enabled them to identify a further 12 variants associated with risk and confirm the association of 18 of the previously published variants; some of the other variants failed to replicate.

In total, there are now known to be 30 risk variants, accounting for 6.5 per cent of the inherited component of risk.

“Ovarian cancer is clearly a very complex disease – even the 30 risk variants that we now know increase risk of developing the disease account for just a small fraction of the inherited component,” says Dr Catherine Phelan from the Moffitt Cancer Center, Tampa, USA. “We believe that there will likely be many more genetic variants involved, each with extremely small effects. Most of these are likely to be common, but some will be rare.”

̽��ֱ��researchers point out that while the common view is of our genes influencing disease risk, in fact most of the variants discovered to date do not fall in our genes, but rather in ‘non-coding’ regions of the human genome, so named because, unlike our genes, they do not provide the code to make proteins. Instead, these regions are often involved in regulating the activity of our genes.

Because the variants are common, some women will carry multiple risk variants. However, even in combination these variants do not have a large effect on risk, say the researchers. Women carrying the greatest number of these risk variants will still have a lifetime risk of ovarian cancer of just 2.8 per cent. To put this into context, family cancer clinics commonly offer surgery to remove the ovaries – and hence prevent the possibility of disease – to women with a lifetime risk of 10 per cent or more.

However, these variants also affect the risk of ovarian cancer in women who carry a fault in the BRCA1 or BRCA2 genes and this might be sufficient to affect the decision of a carrier about when or if to have preventive surgery.

“In some ways, the hard work starts now,” says Dr Simon Gayther from Cedars-Sinai Medical Center, Los Angeles, USA. “We really have little idea of the functional effect these variants have at the molecular or cellular level and so there are few clues as to how they might affect risk. If we can understand how they work, we will be in a better position to treat – and possibly prevent – ovarian cancer.”

̽��ֱ��research was carried out by the Ovarian Cancer Association Consortium and the Consortium of Investigators of Modifiers of BRCA1/2, two consortia that are part of the larger OncoArray Consortium. ̽��ֱ��consortia used a customised Illumina genotyping array, which allowed them to analyse around 533,000 variants and has been used to genotype over 500,000 samples, including the samples in this study of ovarian cancer

Reference
Phelan, CM et al. Identification of twelve novel susceptibility loci for different histotypes of epithelial 1 ovarian cancer. Nature Genetics; 27 Mar 2017; DOI: 10.1038/ng.3826

A genetic trawl through the DNA of almost 100,000 people, including 17,000 patients with the most common type of ovarian cancer, has identified 12 new genetic variants that increase risk of developing the disease and confirmed the association of 18 of the previously published variants.

Gregory Podgorniak

Visualization of DNA sequence invented in 2015

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Scientists double number of known genetic risk factors for endometrial cancer

cjb250 — Tue, 03 May 2016 07:45:36 +0000

Endometrial cancer affects the lining of the uterus. It is the fourth most commonly diagnosed cancer in UK women, with around 9,000 new cases being diagnosed each year.

Researchers at the ̽��ֱ�� of Cambridge, Oxford ̽��ֱ�� and QIMR Berghofer Medical Research Institute in Brisbane studied the DNA of over 7,000 women with endometrial cancer and 37,000 women without cancer to identify genetic variants that affected a woman’s risk of developing the disease. ̽��ֱ��results are published today in the journal Nature Genetics.

Dr Deborah Thompson from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge said: “Our findings help us to paint a clearer picture of the genetic causes of endometrial cancer in women, particularly where there no strong family history of cancer. Prior to this study, we only knew of four regions of the genome in which a common genetic variant increases a woman’s risk of endometrial cancer.

“In this study we have identified another five regions, bringing the total to nine. This finding doubles the number of known risk regions, and therefore makes an important contribution to our knowledge of the genetic drivers of endometrial cancer.

“Interestingly, several of the gene regions we identified in the study were already known to contribute to the risk of other common cancers such as ovarian and prostate.

“Although each individual variant only increases risk by around 10-15%, their real value will be in looking at the total number of such variants inherited by a woman, together with her other risk factors, in order to identify those women at higher risk of endometrial cancer so that they can be regularly checked and be alert to the early signs and symptoms of the disease.”

̽��ֱ��study also looked at how the identified gene regions might be increasing the risk of cancer, and these findings have implications for the future treatment of endometrial cancer patients.

“As we develop a more comprehensive view of the genetic risk factors for endometrial cancer, we can start to work out which genes could potentially be targeted with new treatments down the track,” said Associate Professor Amanda Spurdle from QIMR Berghofer.

“In particular, we can start looking into whether there are drugs that are already approved and available for use that can be used to target those genes.”

̽��ֱ��study was an international collaboration involving researchers from Australia, the United Kingdom, German, Belgium, Norway, Sweden, the United States and China. ̽��ֱ��UK part of the study received funding from Cancer Research UK.

Dr Emma Smith, Cancer Research UK’s science information manager, said: “ ̽��ֱ��discovery of genetic changes that affect women’s risk of developing endometrial – or womb – cancer could help doctors identify women at higher risk, who could benefit from being more closely monitored for signs of the disease.

“It might also provide clues into the faulty molecules that play an important role in womb cancer, leading to potential new treatments. More than a third of womb cancer cases in the UK each year could be prevented, and staying a healthy weight and keeping active are both great ways for women to reduce the risk.”

Reference
Cheng, THT et al. Five endometrial cancer risk loci identified through genome-wide association analysis. Nature Genetics; 2 May 2016; DOI: 10.1038/ng.3562

An international collaboration of researchers has identified five new gene regions that increase a woman’s risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.

Interestingly, several of the gene regions we identified in the study were already known to contribute to the risk of other common cancers

Deborah Thompson

Andy Leppard

DNA representation (cropped)

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First of new generation of cancer drugs granted European approval

cjb250 — Thu, 18 Dec 2014 11:18:19 +0000

̽��ֱ��research that led to the development of the drug began in the mid-1990s in the lab of Professor Steve Jackson at the Wellcome Trust/Cancer Research UK Gurdon Institute at the ̽��ֱ�� of Cambridge. It led to the launch of a university spinout company, KuDOS, which was acquired by pharmaceutical giant AstraZeneca in early 2006.

“This is a success story both for basic science and for UK scientific innovation,” says Professor Jackson. “ ̽��ֱ��initial development of Lynparza would not have been possible without the freedom to pursue our own ideas, driven by our own curiosity, supported by charitable funding. Through our links to industry, this research has led to a considerable commercial opportunity for a UK-based company and a drug that will extend and enhance the lives of various cancer sufferers.

“Lynparza is an innovative new anti-cancer medicine that works in a different way to previously-marketed drugs. Unlike traditional anti-cancer drugs, it makes the cancer cells – not the normal cells of the patient – sick. Today’s development should pave the way for further therapies based on this approach.”

̽��ֱ��drug works by exploiting inherent weaknesses in the mechanism by which DNA is repaired in certain cancer cells, allowing Lynparza to kill cancer cells but not the patient’s healthy cells. Consequently, the drug has fewer side effects than traditional cancer treatments such as radiotherapy or chemotherapies.

Lynparza inhibits the action of an important protein enzyme in human cells called PARP. This enzyme is usually involved in helping cells repair damage to DNA, a crucial process that cells must do to remain alive. Most cells have a back-up repair mechanism known as homologous recombination, which kicks in when PARP is inhibited. However, some cancer cells lack the necessary proteins to carry out this back-up pathway; when PARP is inhibited in such cancer cells, the cancer cells die.

While there are other cancers that can potentially be treated by Lynparza, the drug has initially been approved to treat ovarian cancer patients who have underlying, inherited mutations in the BRCA1 or BRCA2 genes – mutations that prevent homologous recombination. ̽��ֱ��normal cells in these patients have one ‘bad’ copy of the BRCA1 and BRCA2 genes, but still have one normal copy, meaning that they can still do homologous recombination – and hence are still able to carry out vital DNA repair. However, the cancer cells in these patients have lost the normal copy of BRCA1 or BRCA2; they are hence unable to carry out homologous recombination and so Lynparza kills the cancer cells, but not the healthy normal cells.

Clinical trials showed that the new drug, which has relatively mild side-effects compared to traditional anti-cancer agents, extends the progression-free survival of patients compared to those on a control treatment. ̽��ֱ��median progression-free survival was 11.2 months with Lynparza vs 4.3 months with placebo. There was also evidence for extension of overall patient survival.

Professor Jackson’s research has for many years been funded by Cancer Research UK. His group is also supported by grants from the Wellcome Trust, the European Union and the European Research Council.

A new drug for ovarian cancer, developed by researchers at the ̽��ֱ�� of Cambridge and AstraZeneca, has today become the first of new class of drugs, known as PARP-inhibitors, to be granted approval anywhere in the world. ̽��ֱ��drug, Lynparza, has been granted Marketing Authorisation from the European Commission.

This is a success story both for basic science and for UK scientific innovation. ̽��ֱ��initial development of Lynparza would not have been possible without the freedom to pursue our own ideas, driven by our own curiosity, supported by charitable funding

Steve Jackson

PARP-inhibitors: A New Generation of Cancer Drugs

Cancer Research UK

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