Epithelial ovarian cancer

Lhereux, S., Gourley, C.,  Vergote, I.  &Oza, A.  M. | 2019 | Epithelial ovarian cancer| The Lancet| 393 | 10177|p1240- 1253 | doi: https://doi.org/10.1016/S0140-6736(18)32552-2

A new article published in The Lancet looks at the impact of recent developments in the understanding of invasive ovarian cancer.

Summary

Epithelial ovarian cancer generally presents at an advanced stage and is the most common cause of gynaecological cancer death. Treatment requires expert multidisciplinary care. Population-based screening has been ineffective, but new approaches for early diagnosis and prevention that leverage molecular genomics are in development. Initial therapy includes surgery and adjuvant therapy. Epithelial ovarian cancer is composed of distinct histological subtypes with unique genomic characteristics, which are improving the precision and effectiveness of therapy, allowing discovery of predictors of response such as mutations in breast cancer susceptibility genes BRCA1 and BRCA2, and homologous recombination deficiency for DNA damage response pathway inhibitors or resistance (cyclin E1). Rapidly evolving techniques to measure genomic changes in tumour and blood allow for assessment of sensitivity and emergence of resistance to therapy, and might be accurate indicators of residual disease. Recurrence is usually incurable, and patient symptom control and quality of life are key considerations at this stage. Treatments for recurrence have to be designed from a patient’s perspective and incorporate meaningful measures of benefit. Urgent progress is needed to develop evidence and consensus-based treatment guidelines for each subgroup, and requires close international cooperation in conducting clinical trials through academic research groups such as the Gynecologic Cancer Intergroup.
Epithelial ovarian cancer generally presents at an advanced stage and is the most common cause of gynaecological cancer death. Treatment requires expert multidisciplinary care. Population-based screening has been ineffective, but new approaches for early diagnosis and prevention that leverage molecular genomics are in development. Initial therapy includes surgery and adjuvant therapy. Epithelial ovarian cancer is composed of distinct histological subtypes with unique genomic characteristics, which are improving the precision and effectiveness of therapy, allowing discovery of predictors of response such as mutations in breast cancer susceptibility genes BRCA1 and BRCA2, and homologous recombination deficiency for DNA damage response pathway inhibitors or resistance (cyclin E1). Rapidly evolving techniques to measure genomic changes in tumour and blood allow for assessment of sensitivity and emergence of resistance to therapy, and might be accurate indicators of residual disease. Recurrence is usually incurable, and patient symptom control and quality of life are key considerations at this stage. Treatments for recurrence have to be designed from a patient’s perspective and incorporate meaningful measures of benefit. Urgent progress is needed to develop evidence and consensus-based treatment guidelines for each subgroup, and requires close international cooperation in conducting clinical trials through academic research groups such as the Gynecologic Cancer Intergroup.
This article is available to Rotherham NHS staff, request from the Library & Knowledge Service 

Ovarian Cancer Awareness Month

Ovarian Cancer Awareness Month | n.d |  Ovarian Cancer Awareness Month

March is Ovarian Cancer Awareness Month, ovarian cancer is the biggest gynaecological killer of women in the UK women, with UK survival rates among the worst in Europe.

Three quarters of women are diagnosed once the cancer has already spread, making treatment more difficult. This is why awareness is so important, to drive forward improvements in diagnosis, treatment and survival.

Ovarian cancer charities in the UK, we are all working to increase awareness of the disease, with women and GPs, in order to save lives (Source: Ovarian Cancer Awareness Month).

See also:

Ovarian Cancer Action 

The Eve Appeal 

Target Ovarian Cancer

Ovacome 

Sheffield research: New compound could help treat ovarian cancer

University of Sheffield | February 2019 | New compound could help treat ovarian cancer

Two departments at the University of Sheffield have collaborated to explore new drug types that could work against types of treatment resistant cancers. 

Researchers from the Department of Chemistry and the Department of  Biomedical Science have screened new compounds made in the lab against a “panel” of cancers that were sensitive and resistant to standard cancer therapy.

The study’s lead author Professor Jim Thomas, of the Department of Chemistry, said: “Many cancer cells – about 20 per cent – become resistant to common treatments by learning to ignore the internal signals that tell them to undergo programed cell death, known as apoptosis.

“We have identified a compound that kills cancer cells that avoids the need for apoptosis, and so the usual resistance mechanism doesn’t work against our compound.

“The compound is as potent as common current chemotherapeutics, but crucially retains its potency against treatment-resistant cancers. By looking at the cellular response from the cancers we found the new drug lead works by two different mechanisms simultaneously, making it much more difficult for cancers to develop resistance toward them during treatment.

“We think this compound could be particularly effective against ovarian cancer.” (Source: University of Sheffield)

Read the news release in full from University of Sheffield 

Abstract 

Drug resistance to platinum chemotherapeutics targeting DNA often involves abrogation of apoptosis and has emerged as a significant challenge in modern, non-targeted chemotherapy. Consequently, there is great interest in the anti-cancer properties of metal complexes—particularly those that interact with DNA—and mechanisms of consequent cell death. Herein we compare a parent cytotoxic complex, [Ru(phen)2(tpphz)]2+ [phen = 1,10-phenanthroline, tpphz = tetrapyridyl[3,2-a:2′,3′-c:3″,2″-h:2‴,3‴-j]phenazine], with a mononuclear analogue with a modified intercalating ligand, [Ru(phen)2(taptp)]2+ [taptp = 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene], and two structurally related dinuclear, tpphz-bridged, heterometallic complexes, RuRe and RuPt. All three of these structural changes result in a switch from intercalation to groove-binding DNA interaction and concomitant reduction in cytotoxic potency, but no significant change in relative cytotoxicity toward platinum-resistant A2780CIS cancer cells, indicating that the DNA interaction mode is not critical for the mechanism of platinum resistance. All variants exhibited a light-switch effect, which for the first time was exploited to investigate timing of cell death by live-cell microscopy. Surprisingly, cell death occurred rapidly as a consequence of oncosis, characterized by loss of cytoplasmic volume control, absence of significant mitochondrial membrane potential loss, and lack of activation of apoptotic cell death markers. Importantly, a novel, quantitative proteomic analysis of the A2780 cell genome following exposure of the cells to either mononuclear complex reveals changes in protein expression associated with global cell responses to oxidative stress and DNA replication/repair cellular pathways. This combination of multiple targeting modalities and induction of a non-apoptotic death mechanism makes these complexes highly promising chemotherapeutic cytotoxicity leads.

The Library can provide the full article to Rotherham NHS Staff, request here 

Less than half of women are diagnosed with ovarian cancer within a month of seeing a doctor, finds survey

Less than half of women are diagnosed with ovarian cancer within a month of seeing a doctor, finds survey  BMJ 2018363 | k4419|  doi: https://doi.org/10.1136/bmj.k4419 | (Published 18 October 2018)|

Under 50 per cent of women with symptoms that are in common with ovarian cancer are diagnosed within one month of their first visit to a doctor, a large international survey of women with the disease has found. The results also revealed low levels of awareness of the cancer among women and delays in seeking medical help.

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“This study, for the first time, provides powerful evidence of the challenges faced by women diagnosed with ovarian cancer across the world, and sets an agenda for global change,” said Anwen Jones, chief executive officer of Target Ovarian Cancer in the UK and co-chair of the study (Source: BMJ).

The full article is available to Rotherham NHS staff  here 

Combination of new drug and chemotherapy used to treat patients with advanced ovarian and lung cancer

ICR | August 2018 | Drug combination gives ‘exciting’ results in ovarian and lung cancer in early trial

The results of an early clinical trial suggest that a combination of chemotherapy and a new drug could be used to provide treatment for patients with advanced ovarian and lung cancer, where other treatments had failed. 

Scientists from The Institute of Cancer Research, London (ICR), and The Royal Marsden NHS Foundation Trust, decided to test vistusertib, which inhibits the activation of a specific molecule in ovarian cancer cells, to determine if the drug combination was safe for patients, the dosage and its efficacy.  The combination of targeted drug vistusertib along with paclitaxel chemotherapy caused tumours of over 50 per cent of patients with ovarian cancer and over 33 % with lung cancer to shrink, and stopped patients’ cancers from growing for almost six months.

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This far exceeds what is expected with standard treatments in patients with advanced disease who have already had, and have now become resistant to, standard treatment (Source: ICR).

Read the full news release from The Institute for Cancer Research Drug combination gives ‘exciting’ results in ovarian and lung cancer in early trial

In the news:

BBC News Drug cocktail can ‘shrink cancer tumours’

The Times Cancer drug Vistusertib gives hope for terminal patients

Promising new ovarian cancer treatment could soon be available on the NHS

Ovarian Cancer Action | June 2018 |Promising new ovarian cancer treatment could soon be available on the NHS

The National Institute for Health and Care Excellence (NICE) has issued draft guidance on a promising new ovarian cancer drug, niraparib, advising that it is a suitable candidate for use in the Cancer Drugs Fund (CDF) (Ovarian Cancer Action). 

Ovarian cancer is the fifth most common cause of cancer death in women and has the highest mortality rate of all gynaecological cancers. Five-year survival in England and Wales is also among the lowest in Europe – well below the European average. While these figures are bleak, it is exciting to think that niraparib could provide a much-needed new option for many women with the disease.

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“We are pleased that the NICE committee has recognised the high unmet need in ovarian cancer treatment,” said Katherine Taylor, Chief Executive of Ovarian Cancer Action. “Every day matters for patients and their families and we hope that the CDF submission is successful and will deliver access to many women in England and Wales as soon as possible. We also look forward to a review by the Scottish Medicines Consortium (SMC) later this year.”

Source: Ovarian Cancer Action

Related:

NICE Niraparib for ovarian cancer [ID1041]

In the media:

The Independent Ovarian cancer ‘game changer’ drug which holds back disease’s return gets first NHS fund approval

Sky News Niraparib drug: Daily pill available on NHS for first time is ‘milestone’ in ovarian cancer treatment

Express Ovarian cancer – ‘game changing’ new drug puts patient’s tumour into remission

Gene on the X-chromosome may contribute to a woman’s risk of developing ovarian cancer according to US researchers

Currently, women with a strong family history of cancer can be tested for the BRCA gene, which greatly increases a woman’s chance of developing breast cancer and ovarian cancer. Yet experts believe there may be other cases of sporadic ovarian caner that are inherited via the X chromosome females receive from their father.  Full story at BBC News 
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US researchers have used the largest familial study of ovarian cancer to argue that there exists an ovarian cancer susceptibility gene on the X-chromosome acting independently of BRCA1 and BRCA2. This observation implies that there may be many cases of seemingly sporadicovarian cancer that are actually inherited; for example, only daughters who inherit risk from their fathers. This X-linked pattern implies novel ways to prioritize families for screening even without additional testing-sisters must both be carriers or neither; fathers of women with potentially inherited ovarian cancer may receive new attention.
In addition, the scientists found evidence that other cancers affect fathers and sons in these families. Using sequencing technology, we isolated a candidate gene, MAGEC3, that may be associated with earlier onset of ovarian cancer. The further study of this gene and the X-linked pattern will require additional study.  (Author summary from PLOS Genetics)

Full reference: Eng, K. H. 2018||Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study|PLOS Genetics| https://doi.org/10.1371/journal.pgen.1007194

The article can be downloaded from PLOS here 

Related content:  Daily Telegraph  Ovarian cancer can be passed on via fathers – and it strikes younger