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 

Leeds research: Smoking may limit body’s ability to fight skin cancer

University of Leeds | February 2019 | Leeds research: Smoking may limit body’s ability to fight skin cancer

A study of more than 700 melanoma patients, mainly from the north of England, provides evidence to suggest that smoking may blight the immune response against melanoma and reduce survival.

The study led by experts at the University of Leeds found that people diagnosed with melanoma who also smoked/ had history of smoking are 40 per cent less likely to survive their melanoma than non-smokers within a decade of diagnosis.

smoke-298243_640.jpg

In a subset of 156 patients who had the most genetic indicators for immune cells, smokers were around four and a half times less likely to survive from the cancer than people who had never smoked.

Lead author Julia Newton-Bishop, Professor of Dermatology at the University of Leeds, said: “The immune system is like an orchestra, with multiple pieces. This research suggests that smoking might disrupt how it works together in tune, allowing the musicians to continue playing but possibly in a more disorganised way.

“The result is that smokers could still mount an immune response to try and destroy the melanoma, but it appears to have been less effective than in never-smokers, and smokers were less likely to survive their cancer.

“Based on these findings, stopping smoking should be strongly recommended for people diagnosed with melanoma.” (Source: University of Leeds)

Read the press release from the University of Leeds 

This study was funded by Cancer Research UK and has been published in the journal Cancer Research

Pozniak, J. et al.| 2019| Genetic and environmental determinants of immune response to cutaneous melanoma| Cancer Research| DOI: 10.1158/0008-5472.CAN-18-2864

Quality of life in men living with advanced and localised prostate cancer in the UK: a population-based study

Downing, A. et al |2019|Quality of life in men living with advanced and localised prostate cancer in the UK: a population-based study| The Lancet Oncology|https://doi.org/10.1016/S1470-2045(18)30780-0

A new piece of research that examines the quality of life for UK men living with advanced and localised prostate has been published in The Lancet Oncology

Summary

Background

Little is known about the health-related quality of life (HRQOL) of men living with advanced prostate cancer. We report population-wide functional outcomes and HRQOL in men with all stages of prostate cancer and identify implications for health-care delivery.

 

Methods

For this population-based study, men in the UK living 18–42 months after diagnosis of prostate cancer were identified through cancer registration data. A postal survey was administered, which contained validated measures to assess functional outcomes (urinary incontinence, urinary irritation and obstruction, bowel, sexual, and vitality and hormonal function), measured with the Expanded Prostate Cancer Index Composite short form (EPIC-26), plus questions about use of interventions for sexual dysfunction) and generic HRQOL (assessed with the 5-level EuroQol five dimensions questionnaire [EQ-5D-5L] measuring mobility, self-care, usual activities, pain or discomfort, and anxiety or depression, plus a rating of self-assessed health). Log-linear and binary logistic regression models were used to compare functional outcomes and HRQOL across diagnostic stages and self-reported treatment groups. Each model included adjustment for age, socioeconomic deprivation, and number of other long-term conditions.

 

Findings

35 823 (60·8%) of 58 930 men responded to the survey. Disease stage was known for 30 733 (85·8%) of 35 823 men; 19 599 (63·8%) had stage I or II, 7209 (23·4%) stage III, and 3925 (12·8%) stage IV disease. Mean adjusted EPIC-26 domain scores were high, indicating good function, except for sexual function, for which scores were much lower. Compared with men who did not receive androgen deprivation therapy, more men who received the therapy reported moderate to big problems with hot flushes, low energy, and weight gain. Poor sexual function was common, regardless of stage, and more than half of men were not offered any intervention to help with this condition. Overall, self-assessed health was similar in men with stage I–III disease, and although slightly reduced in those with stage IV cancer, 23·5% of men with metastatic disease reported no problems on any EQ-5D dimension.

Interpretation

Men diagnosed with advanced disease do not report substantially different HRQOL outcomes to those diagnosed with localised disease, although considerable problems with hormonal function and fatigue are reported in men treated with androgen deprivation therapy. Sexual dysfunction is common and most men are not offered helpful intervention or support. Service improvements around sexual rehabilitation and measures to reduce the effects of androgen deprivation therapy are required.

 

Funding

The Movember Foundation, in partnership with Prostate Cancer UK.

The full article can be requested by Rotherham NHS staff here 

 

In the news:

NICE draft guidance recommends pertuzumab for new breast cancer indication after improved price offer from company

NICE | February 2019 | NICE draft guidance recommends pertuzumab for new breast cancer indication after improved price offer from company

NICE has published final draft guidance recommending pertuzumab (Perjeta, Roche) for treating early HER2-positive breast cancer in people whose disease has spread to their lymph nodes.

This positive recommendation is for people who have had surgery for their breast cancer and whose cancer has already spread to their lymph nodes. The estimated 2700 people in this subgroup have a higher risk of their cancer returning.

The evidence shows that adding pertuzumab to trastuzumab and chemotherapy after surgery increased the proportion of people whose disease didn’t spread. However, there is a lack of evidence on how long, if at all, adding pertuzumab might increase the overall length of time people live.

Final guidance is expected to be published in March (Source: NICE).

The full details are available from NICE 

National Lung Cancer Audit: Clinical Outcome Publication Report 2018

Health Quality Improvement Programme | February 2019 | National Lung Cancer Audit: Clinical Outcome Publication Report 2018

Health Quality Improvement Programme (HQIP) have produced the fifth report on the individual activity of surgeons and their contribution to lung cancer care. The data relate to patients diagnosed with lung cancer who underwent surgery during the period between 1 January and 31 December 2016.

hqip
Image source: hqip.org.uk

In addition to publishing the number of operations performed by hospitals and by individual consultant surgeons, the following outcomes are reported:

  • the proportion of patients who survive at 30 days, 90 days and 1 year after their operation for each unit
  • the median length of stay in hospital following an operation
  • the proportion of patients who were readmitted within 90 days of hospital discharge
  • the pooled resection rates for the lung cancer team meetings (MDTs) which a surgical unit serves (Source: HQIP)

Download the full report from HQIP.

National Prostate Cancer Audit: Annual Report 2018

Health Quality Improvement Partnership | February 2019 | National Prostate Cancer Audit: Annual Report 2018

Health Quality Improvement Partnership (HQIP) have published the results of their national prostate cancer audit in the report National Prostate Cancer Audit: Annual Report 2018.

There are over 40,000 new diagnoses of prostate cancer every year in the UK and over 11,000 men die because of the disease. This makes prostate cancer the second most common cause of cancer-related death for men in the UK.

cancer
Image source: hqip.org.uk

 

This report presents results for men diagnosed with prostate cancer between 1st April 2016 and 31st March 2017 in England and Wales. It reports on specific diagnostic, staging and treatment information as well as core performance indicators in order to compare diagnostic specialist MDTs or treatment centres. This is the first report which combines English and Welsh data as well as using patient-reported experience (PREMs) and outcome measures (PROMs) as performance indicators.

Reporting on a total of 14 performance indicators, the NPCA is the first national audit which is able to report on process and outcome measures from all aspects of the care pathway for men with prostate cancer (Source: HQIP).

Download it from HQIP