Immune cell discovery opens up possibility of new treatment for blood cancer

Researchers have unlocked the secrets of a little-understood immune cell, potentially paving the way for an easier way to treat and prevent graft-versus-host disease (GVHD).

GVHD occurs in up to 70 per cent of patients who receive a stem cell transplant to treat blood cancer. It is caused by donated immune cells (called T cells) attacking tissue in the recipient’s skin, gastrointestinal tract, liver or lungs. Unfortunately, a significant proportion of patients who develop acute GVHD of the gastrointestinal tract do not survive.

Regulatory T cells play vital role

QIMR Berghofer senior scientist Professor Geoff Hill, lead author Dr Ping Zhang, and their team have discovered that a type of T cell known as a type 1 regulatory T cell, or TR1 cell, plays a crucial role in fighting GVHD.

Importantly, they have also discovered the protein that causes these cells to develop, allowing them to produce TR1 cells in large numbers in the laboratory.

Professor Hill said that while conventional T cells fight disease and infection, regulatory T cells are responsible for keeping a check on immune responses and preventing them from causing harm.

“Regulatory T cells are particularly important for stem cell transplant recipients because they stop the donor cells from mounting an immune response against normal tissues,” Professor Hill said.

“There are two types of regulatory T cells: FoxP3 regulatory T cells, and TR1 cells.”

“In most cases, FoxP3 regulatory T cells are more important and exist in much higher numbers than TR1 cells. But in this study, we found that TR1 cells are very important in stem cell transplantation.”

“Patients with GVHD stop being able to make FoxP3 regulatory T cells and therefore have very low numbers of these cells. However, we found that when their levels decline, TR1 cells increase in number and become critical in stopping donor cells from attacking host tissues.”

“In other words, TR1 cells compensate when FoxP3 regulatory T cells either fail or can’t be made.”

Protein helps identify cells in patients

Dr Zhang said the researchers had also identified the particular protein that controls the development of TR1 cells.

“Knowing which protein controls the development of these cells means we can now find them easily in patients, and we’ve also been able to generate them in the laboratory,” he said.

Professor Hill said that it was also very exciting that the abundance of TR1 cells could be changed by specific signals delivered by molecules known as cytokines.

“It is probable that some of the therapies we are investigating in clinical trials induce TR1 T cells, and we are now able to examine this in our patients,” he said.

“Also, now that we understand more about how TR1 cells are produced and what they do, we hope to be able to generate them and give them to stem cell transplant patients to prevent GVHD.”

“This is already being done with FoxP3 regulatory T cells, but we think it will be easier to do with TR1 cells.”

“We hope that by giving patients infusions of these cells early on, we will eventually be able to prevent GVHD altogether.”

The findings have been published in the journal Science Immunology.

The study was funded by the National Health and Medical Research Council (NHMRC).

This news article was first posted on the QIMR Berghofer website.

The Australian Cancer Research Foundation has supported cancer research at QIMR Berghofer by providing three grants, totalling AUD$ 6.65 M, for the purchase of cutting edge research equipment and technology.

World-first liquid biopsy for blood cancers to improve treatment

A simple blood test to monitor blood cancers will soon be available to more than 12,000 Australians diagnosed with blood cancers each year.

Researchers at Peter MacCallum Cancer Centre in Melbourne have recently developed the world-first ‘liquid biopsy’, which promises a new era of less invasive, more precise and effective management of blood cancers, in place of painful bone marrow or lymph node biopsies.

Published this month in both Nature Communications and Blood, the study shows how liquid biopsies can be applied in clinical cases of chronic lymphocytic leukaemia and myelodysplastic syndromes.

The liquid biopsy, developed by Associate Professor Sarah-Jane Dawson and Professor Mark Dawson, monitors tiny fragments of DNA emitted from cancer cells into the blood stream, called circulating tumour DNA (ctDNA).

Unlike traditional biopsies, ctDNA tests:

  • track disease status throughout the body
  • can be used at any time over the course of cancer treatment
  • enable rapid adjustments if a patient relapses or fails to respond to a particular therapy.

A/Professor Sarah-Jane Dawson has helped pioneer the development of ctDNA tests for solid tumours in breast and other cancer types, which now guide the treatment of some 500 patients who are part of her research program.

A/Professor Dawson says this world-first ctDNA test for blood cancers will also help to more rapidly advance the availability of new precision medicines and targeted therapies as these are developed.

“Not only does this new test promise clinicians and patients a more timely and accurate understanding of whether a cancer treatment is working, it gives scientists the ability to quickly and effectively evaluate how clinical trial patients are responding to new life-saving therapies.”

Improved blood cancer test accuracy

Professor Mark Dawson says the liquid biopsy also addresses one of the major limitations of the current approach to managing blood cancers.

“We know that a single tissue biopsy from the bone marrow or lymph node does not accurately reflect the composition of the whole tumour as there is significant variation – so called intra-tumour heterogeneity – that exists between the individual cells that make up any cancer.”

“Because cancer cells from all disease sites within the body shed their DNA into the bloodstream, we found that ctDNA collected from a routine blood sample more accurately mirrors the disease across all parts of the body.”

“This ctDNA test for blood cancer therefore provides a much more comprehensive picture of how a patient is responding to their treatment,” Professor Dawson said.

The ctDNA tests from Peter Mac will be available to patients within Australia from late 2017 and are expected to become a standard clinical tool in the near future.

This research was supported by the National Health and Medical Research Council of Australia; Leukaemia and Lymphoma Society USA; Victorian Cancer Agency; National Breast Cancer Foundation; Leukaemia Foundation Australia; Snowdome Foundation; and the Haematology Society of Australia and New Zealand. Core technologies for the research are supported by the Australian Cancer Research Foundation and Peter MacCallum Cancer Centre.

The news article was first published on the Peter Mac website. Image courtesy of Peter Mac.

The Australian Cancer Research Foundation (ACRF) has supported Peter Mac by providing three grants, totalling AUD $7 million towards cutting edge cancer research equipment and technology. In 2016, ACRF awarded a $2 million grant to a Peter Mac-led consortium of members of the Victorian Comprehensive Cancer Centre to establish the ACRF Tumour Heterogeneity Program. The new program will be led by A/Professor Sarah-Jane Dawson.

New pathway for blood cancer therapies

Cancer researchers at Peter MacCallum Cancer Centre and Monash University in Melbourne have identified for the first time how a new class of epigenetic drug engages with the immune system to kill off cancer cells.

The research, published in journal Cell Reports, has demonstrated the potential of combining ground-breaking epigenetic and immune-based treatments for improved results.

The experiments showed that immune-competent mice with lymphoma had a far greater response to BET-inhibitors than their immune-deficient counterparts. BET-inhibitors are a relatively new class of cancer treatment, which work to ‘switch off’ important cancer-causing genes expressed within tumour cells.

In addition to the improved response, the research showed that BET inhibitors were able to ‘switch off’ a protein called PD-L1 which is used by tumour cells to hide from the immune system.

Through this mechanism, BET-inhibitors were making tumour cells more sensitive to attack from the immune system.

The power of an activated immune system in eliminating tumour cells has been proven through successful drugs such as Keytruda and Opdivo, which also target the PD-L1 pathway.

Building on this knowledge, Melbourne researchers confirmed that the combinations of BET-inhibitors with other immune therapies work better in lymphoma than either therapy alone.

Based on laboratory research performed at Peter Mac, the Monash team is currently trialling a combination of a different epigenetic drug called Dinaciclib with the anti-PD1 therapy, Keytruda, in relapsed lymphoma, myeloma and chronic lymphocytic leukaemia. Further clinical trials for the combination therapy are likely to emerge as a result of this research.

This research was supported by the National Health and Medical Research Council of Australia; Victorian Cancer Agency; Snowdome Foundation; Cancer Council Victoria; The Kids Cancer Project, and Roche. Core technologies enabling the research are supported by the Australian Cancer Research Foundation (ACRF) and Peter MacCallum Cancer Foundation.

This article was first published on the Peter Mac website, image courtesy of Peter Mac.

To date, ACRF has awarded in total $AUD 8.2 million to support cancer research at Peter MacCallum Cancer Centre and Monash University.

New blood cancer centre to improve patient outcomes

Alfred Health and Monash University are set to establish Australia’s first dedicated blood cancer research centre, thanks to a $1.2 million grant from the Australian Cancer Research Foundation (ACRF).

The ACRF Blood Cancer Therapeutics Centre, based at The Alfred, will be home to the latest technology available in blood cancer research and will enable researchers to dramatically improve outcomes for patients with blood cancer.

Each year, 11,500 Australians are diagnosed with blood cancer, including leukaemia, lymphoma and myeloma. Sadly, these debilitating diseases – which account for one in 10 cancers diagnosed nationally – claim 4000 lives every year.

Dr Andrew Wei, haematologist at The Alfred and Monash University, said the new centre will enable researchers to find out more about these cancers – including why some treatments work for some people and others don’t – and develop new ways to treat them.

“Many of our patients with various forms of blood cancer have had great success in clinical trials, which use new and unique drug combinations,” Dr Wei said.

“Utilising the most up to date technology available, this new centre will enable us to discover more effective therapies, track patient treatment responses up to 1000 times more closely, and improve therapies to get better outcomes overall for patients.

“Blood cancers are relatively neglected when it comes to research. Thanks to this grant, Monash University and The Alfred will be at the forefront of blood cancer research – it is the only way we can improve outcomes for people diagnosed with blood cancer.”

The flagship centre will collect samples from across the country. It is one of only four projects nationally to receive an ACRF grant this year.

“This project encompasses a virtuous cycle of drug discovery, validation, personalised molecular monitoring and improvement of new treatment combinations. It is something ACRF feels has the potential to become a flagship success,” said Australian Cancer Research Foundation CEO Professor Ian Brown.

Cover image: Prof Andrew Wei and His Excellency General The Honourable David Hurley AC DSC (Ret’d), Governor of New South Wales

Protein discovery leads to tablet that “melts away blood cancer”

A potent anti-cancer treatment co-developed and trialled in Melbourne was granted approval for use in patients by the US Food and Drug Administration (FDA) in April 2016.

The approval was announced this week and it recognises that the drug, venetoclax, is a successful new therapy for patients with chronic lymphocytic leukaemia (CLL). CLL is one of the most common forms of leukaemia in Australia and the Western hemisphere – it accounts for approximately one-third of new leukaemia cases.

Venetoclax was developed based on a landmark discovery in 1988 by Walter and Eliza Hall Institute (WEHI) scientists. They found that a protein called BCL-2 promoted cancer cell survival. Ever since, scientists around the world have been trying to find a way to target BCL-2 as a treatment for certain cancers.

Cancer researchers at WEHI

A team effort by WEHI researchers.

Professor Andrew Roberts, a clinical haematologist and head of clinical translation at WEHI said trials had shown patients responded to venetoclax with a very substantial reduction of leukaemia cells in their body.

“Some patients have remained in remission four years after their treatment began,” Professor Roberts said of the trials.

“In many cases we have seen the cancerous cells simply melt away.”

The drug is effective in killing cancer cells in approximately 80 per cent of people with very advanced forms of CLL. Twenty per cent of patients achieved a complete remission, where the leukaemia was no longer seen on routine tests. The US approval is for patients with CLL who have a specific chromosomal abnormality called a 17p deletion and who have been treated with at least one other therapy.

Professor Roberts said a small number of patients had such a profound response to venetoclax that even very sensitive research tests were unable to detect any remaining leukaemia in their bodies.

WEHI Director, Professor Doug Hilton said the development of venetoclax had set the foundation for building towards the “dream of a cure for CLL”. It reflects the critical importance of robust medical research funding in Australia and worldwide cialis overnight delivery.

“Research that ultimately leads to major advances and cures can take decades to be developed and venetoclax is representative of that trajectory,” Professor Hilton said.

More than 100 WEHI staff and students have been involved in the development of venetoclax and it was co-developed for use by two US pharmaceutical companies.

The original news post was published on the WEHI website. Image of

The Australian Cancer Research Foundation (ACRF) has supported cancer research at WEHI by providing three research grants, AUD$ 5.5M in total. The establishment of the ACRF Centre for Therapeutic Target Discovery at WEHI assisted with this discovery and has supported scientists in testing primary human samples against a range of drugs.

Blood cancer gene discovery

A genetic discovery from Professor Hamish Scott and his research team at the Centre for Cancer Biology (CCB) will help to identify and monitor people at very high risk of developing blood cancers such as leukaemia and lymphoma.

An article published in the haematology journal Blood, presents a major breakthrough for families with a history of blood cancers. The research team pinpointed mutations in the gene DDX41 as significant in families where myelodysplastic syndrome, acute myeloid leukaemia and lymphoma are common.

The research, using the very latest gene sequencing technologies, is part of an international collaboration with the cancer research team at the University of Chicago which discovered mutations in the DDX41 gene.

“This is the first gene identified in families with lymphoma and represents a major breakthrough for the field,” Prof Scott said.

“Researchers are recognising now that genetic predisposition to blood cancer is more common than previously thought, and our study shows the importance of taking a thorough family history at diagnosis.”

“Often the first symptoms of blood cancer don’t occur until the disease is advanced, so the opportunity to diagnose people at high risk will save lives.”

“DDX41 is a new type of cancer predisposition gene and we are still investigating its function, but it appears to have dual roles in regulating the correct expression of genes in the cell and also enabling the immune system to respond to threats such as bacteria and viruses, as well as the development cancer cells,” Prof Scott continued.

“Immunotherapy is a promising approach for cancer treatment and our research to understand the function of DDX41 will help design better therapies.”

“This kind of research is only possible through the collaboration of many groups and we are fortunate to have access to world class facilities through the Australian Cancer Research Foundation Cancer Genomics Facility at the CCB, the willing participation of families living with blood cancer and the support of the Clinical Genetics Service at SA Pathology,” Dr Scott said.

This research has been supported by the National Health and Medical Research Council (NHMRC) of Australia, the Cancer Council of South Australia, the Leukaemia Foundation and the University of South Australia.

This news article was originally published by CCB. Image of Dr Scott and his team courtesy of CCB.

The Australian Cancer Research Foundation has supported CCB by providing two grants, totalling AUD 5.5million, towards cutting edge cancer research equipment and technology.

New targeted therapies for patients with advanced blood cancers

Researchers at the Peter MacCallum Cancer Centre in Melbourne are pioneering the development of a new combination drug therapy to treat advanced blood cancers.

The new therapy builds on a world-first clinical trial already underway at Peter Mac, which uses the drug CX-5461 to treat patients with incurable blood cancers such as myeloma, lymphoma and leukaemia.

The new discovery, published in the journal Cancer Discovery, has shown promising results to date. The research team has found that CX-5461 could be even more effective when used in combination with another drug, Everolimus, already used to treat other cancers. The new combination has shown doubled survival times in pre-clinical laboratory models.

Killing off drug therapy resistant cancer cells

According to Professor Rick Pearson, Head of Peter Mac’s Cancer Signalling Laboratory, the research findings significantly enhance understanding of pre-emptive strategies to kill off cancer cells before they have the chance to become resistant to therapy.

“CX-5461 targets a particular process that is required for cancer cell survival. Our experiments show that adding Everolimous synergistically strengthens this attack, more rapidly and more effectively eradicating the killer disease.”

“We know that all cells rely on ribosomes (protein builders of the cell Ed.) which act like a factory producing the proteins essential for their growth and survival,” said Professor Pearson.

“Peter Mac researchers have previously shown that certain blood cancers are far more reliant on these proteins than normal cells, and that eliminating the protein production capability of ribosomes leads to the rapid death of cancer cells, while normal cells stay viable.”

“This novel therapy works to inhibit the ribosomes’ protein production capability, effectively starving the cancer cells of a key ingredient they need to survive and proliferate.”

“A further study in collaboration with scientists at Monash University shows striking effects in the targeting of late stage prostate cancer through a similar strategy indicating that this approach may be generally applicable for a range of cancer types.”

New leukaemia treatment

Cell death shown in combination therapy trials.

Improving outcomes for blood cancer patients

Associate Professor Simon Harrison, Consultant Haematologist at Peter Mac and Principal Investigator on the CX-5461 first-in-human trial, says this new research provides further confidence that researchers are on the right track.

“The prevalence and poor prognosis for people with advanced blood cancers demands the ongoing and intricate study of abnormal cell behaviour, which has been an indicator of cancer for over 100 years. To date 15 patients have been treated on the first-in-human clinical study with a number of patients experiencing prolonged benefit.”

More than 12,000 Australians are diagnosed with blood cancer annually (approximately 10% of all cancers) and around 4,000 Australians will lose their lives to the disease each year.

This research is supported by the National Health and Medical Research Council; Cancer Council Victoria; the Leukemia Foundation; Prostate Cancer Foundation of Australia; Cancer Australia; Victorian Cancer Agency, Australian Cancer Research Foundation and Peter MacCallum Cancer Foundation. Collaborators include the John Curtin School of Medical Research at the Australian National University and Monash University.

The Australian Cancer Research Foundation has supported cancer research at Peter Mac by providing three major grants, totalling AUD 7 million.

The news was originally published on Peter Mac’s website.

Images courtesy of Peter Mac. On the cover Professor Rick Pearson with Professor Ross Hannan, Australian National University.

Top image: istockphoto. com

New blood test can detect eight different cancers in their early stages

Researchers have developed a blood test that can detect the presence of eight common cancers. Called CancerSEEK, the blood test detects tiny amounts of DNA and proteins released into the blood stream from cancer cells. This can then indicate the presence of ovarian, liver, stomach, pancreatic, oesophageal, bowel, lung or breast cancers.

Known as a liquid biopsy, the test is distinctly different to a standard biopsy, where a needle is put into a solid tumour to confirm a cancer diagnosis. CancerSEEK, is also far less invasive. It can be performed without even knowing a cancer is present, and therefore allow for early diagnosis and more chance of a cure.

Read more – Interactive body map: what really gives you cancer?

The test has been shown to reliably detect early stage and curable cancers. It has also been found to rarely be positive in people who don’t have cancer. This prevents significant anxiety and further invasive tests for those who don’t need them.

Several cancers can be screened for at once, and the test can be performed at the same time as routine blood tests, such as a cholesterol check. But the test is still some years away from being used in the clinic.

How the test works

Often long before causing any symptoms, even very small tumours will begin to release minute amounts of mutated DNA and abnormal proteins into blood. While DNA and proteins are also released from normal cells, the DNA and proteins from cancer cells are unique, containing multiple changes not present in normal cells.

The newly developed blood-based cancer DNA test is exquisitely sensitive, accurately detecting one mutated fragment of DNA among 10,000 normal DNA fragments, literally “finding the needle in the haystack”.

Tumours release mutated DNA and abnormal proteins into blood.

We used CancerSEEK in just over 1,000 people with different types of early stage cancers. It was shown to accurately detect the cancer, including in 70% or more of pancreas, ovary, liver, stomach and esophageal cancers. For each of these tumour types there are currently no screening tests available – blood based or otherwise.

Along with cancer detection, the blood test accurately predicted what type of cancer it was in 83% of cases.

Published in the journal Science, the research was led by a team from John Hopkins University, with collaboration from Australian scientists at the Walter and Eliza Hall Institute.

Why it’s important

Steady progress continues to be made in the treatment of advanced cancers, including major gains in life expectancy. But this can come at significant physical and financial cost. Early diagnosis remains the key to avoiding the potentially devastating impact of many cancer treatments and to reducing cancer deaths.

However, where there are proven screening tests that lead to earlier diagnosis and better outcomes, such as colonoscopy screening for bowel cancer, these are typically unpleasant. They also have associated risks, only screen for one cancer at a time and population uptake is often poor. And for many major tumour types there are currently no effective screening tests.

Read more: Can we use a simple blood test to detect cancer?

There are characteristic patterns of mutations and altered proteins that differ among cancer types. So CancerSEEK can not only detect that there is a cancer somewhere in the body but can also suggest where to start looking.

For example, if the pattern suggests a bowel cancer, then a colonoscopy is a logical next step. When blood samples were taken from over 800 apparently healthy controls, less than 1% scored a positive test. This means the test is rarely positive for people who don’t have cancer, thereby reducing the problem of overdiagnosis.

Overall, these results appear to be in stark contrast to previously developed blood-based tests for cancer screening. Currently the only widely used one of is the prostate specific antigen (PSA) test for prostate cancer. This has multiple limitations and some would argue the jury is still out on whether PSA based testing does more good than harm.

Read more: Four reasons I won’t have a prostate cancer blood test

What next?

Large trials are now underway in the US, with CancerSEEK testing being offered to thousands of healthy people. Cancer incidence and outcomes in these people will be compared to a control group who do not have testing. Study results will be available in the next three to five years.

The Conversation

Peter Gibbs received funding from NHMRC that supported some of the research described.

Bladder cancer deaths show why blood in urine should always be investigated

Bladder cancer affects almost 3,000 Australians each year and causes thousands of deaths. Yet it often has a lower profile compared to other types of cancer such as breast, lung and prostate.

The rate at which Australians are diagnosed with bladder cancer has decreased over time, which means the death rate has fallen too, although at a slower rate. This has led to an increase in the so called mortality-to-incidence ratio, a key statistic that measures the proportion of people with a cancer who die from it.

For bladder cancer this went up from 0.3 (about 30%) in the 1980s to 0.4 (40%) in 2010 (compared to 0.2 for breast and colon cancer and 0.8 for lung cancer). While the relative survival (survival compared to a healthy individual of similar age) for most other cancers has improved in Australia, for bladder cancer this has decreased over time.

Who gets bladder cancer?

Environmental risk factors are thought to be more important than genetic or inherited susceptibility when it comes to bladder cancer. The most significant known risk factor is cigarette smoking.

Australia’s anti-smoking measures and effective quitting campaigns have led to a progressive reduction in smoking rates over the last 25 years. This is undoubtedly one key reason behind the observed decline in bladder cancer diagnoses over time.

Bladder cancer risk also increases with exposure to chemicals such as dyes and solvents used in industries like hairdressing, printing and textiles. Appropriate workplace safety measures are crucial to minimising exposure, but the increased risk of occupational bladder cancer remains an ongoing problem.

Certain medications, such as the chemotherapy drug cyclophosphamide, and pelvic radiation therapy have also been linked to bladder cancer. Patients who have had such treatment need to be specifically checked for the main symptoms and signs of bladder cancer, such as blood in urine.

Men develop bladder cancer about three times as often as women. In part, this may have to do with the fact that men are exposed more to the risk factors. Conversely, women have a relatively poorer survival from bladder cancer compared to men. The reasons for this are unclear, but may partly relate to difficulties in diagnosis.

Read more – Interactive body map: what really gives you cancer?

How is bladder cancer diagnosed?

At present, unlike other cancers such as breast cancer that can be picked up on mammograms, bladder cancer can’t be diagnosed at the stage where there are no symptoms. The usual symptoms that lead to the diagnosis of bladder cancer are blood in the urine (haematuria) or irritation during urination, such as frequency and burning.

But symptoms are quite common and, in most instances, caused by relatively benign problems such as infections, urinary stones or enlargement of the prostate. So, the key to bladder cancer diagnosis is for suspicious symptoms to be quickly and appropriately assessed by a doctor.

Haematuria, in particular, always needs to be considered a serious symptom and investigated further. Up to 20% of patients with blood in the urine will turn out to have bladder cancer. Even if the bleeding occurs transiently, this could still be the first symptom that leads to the earliest possible diagnosis of bladder cancer. It shouldn’t be ignored, since delayed diagnosis of bladder cancer is known to worsen treatment outcomes.

Blood in urine always need to be considered a serious symptom and investigated further.

Unfortunately, delays in investigation of blood in urine are well known to occur and particular subgroups such as women and smokers tend to experience the greatest delays.

Recent studies from Victoria and West Australia have shown how some Australian patients have significant and concerning delays in investigation of urinary bleeding. Multiple factors contribute to such delays, including public perception and anxiety, lack of referral from general practitioners and administrative and resourcing limitations at hospitals.

Patients reporting blood in their urine should be referred for scans such as an ultrasound or computerised tomography (CT) to assess the kidneys. They should also have their bladder examined internally (cystoscopy) using a fibre-optic instrument known as a cytoscope. Cystoscopy, a procedure usually performed by urologists (medical specialists of urinary tract surgery), remains the gold standard for diagnosing bladder cancer.

Although diagnostic scans can help detect some bladder cancers, they have significant limitations in detecting certain types of tumours.

What happens if cancer is detected?

If a bladder cancer is noted on cystoscopy, it is removed and/or destroyed using instruments that can be passed into the bladder alongside the cystoscope. These procedures can be carried out at the same setting or subsequently, depending on available instruments and anaesthesia.

The cancerous tissue removed is examined by a pathologist to confirm the diagnosis. This also provides additional information such as the stage of the cancer (how deep it has spread) and grade (based on appearance of the cancer cells), which help determine further management.

Are there any new developments?

Given that cystoscopy is an invasive procedure, there has been considerable effort to develop a non-invasive test, usually focusing on markers in the urine that can indicate the presence of cancer. To date, none of these have been reliable enough to obviate the need for cystoscopy.

Read more: Can we use a simple blood test to detect cancer?

Additionally, to enhance the ability to detect small bladder cancers, cystoscopy using blue light of a certain wavelength (360-450nm) can be combined with the administration of a fluorescent marker (hexaminolevulinate) which highlights the cancerous tissue. While this approach does lead to the detection of more cancers, the resulting clinical benefit remains uncertain.

At present, immediate and appropriate investigation of suspicious symptoms, especially haematuria, using a combination of radiological scans and cystoscopy, remains the best means to diagnose bladder cancer in an accurate and timely manner.

The Conversation

Shomik Sengupta receives funding from Cancer Australia as co-investigator on bladder cancer clinical trials.
He is affiliated with Monash University as Professor of Surgery at the Eastern Health Clinical School, with the Urological Society of Australia and New Zealand as the leader of the Genito-Urinary Oncology Special Advisory Group, and with the Australian and New Zealand Urogenital and Prostate cancer trials group as a Board Director, member of the Scientific Advisory Committee and deputy-chair of the bladder cancer subcommittee.

Can we use a simple blood test to detect cancer?

Breast cancer could be detected using a blood test, according to reports out yesterday. Scientists at the Australian National University (ANU) are working with counterparts in France to make this form of cancer detection, that is far less invasive and expensive than other tests such as biopsies, a reality.

Researchers say they’ll be able to test for breast cancer in blood by checking the proportion of certain isotopes, carbon-13 and nitrogen-15 – which are variants of particular chemical elements – in a tissue sample. This can reveal whether the tissue is healthy or cancerous.

But the test is still around ten years away from being used in the clinic, although research in this area is booming. Scientists have been looking for, and finding, ways to track various cancers in blood for some time. Indeed, blood-based testing for solid tumours in not a new development.

Currently, some tests are used to detect proteins found in higher levels in certain types of cancer. These are called “tumour markers” and include CA15-3 in breast cancer, CA19-9 in pancreatic cancer and CA-125 in ovarian cancer.

However they are relatively unspecific. For instance, a person with ovarian cancer will have high levels of CA-125, but high levels don’t always mean the person has ovarian cancer. They could indicate a benign tumour on the ovary instead. Nor can these tests assess how the cancer changes over time. So how are the new blood tests being developed to hit the target?

First, a bit about cancer

Cancer is a disease of the genome, which means it’s characterised and caused by changes in our genes that can drive a healthy cell to mutate into a cancerous one.

Cancer remains difficult to treat because each cancer is different, even within the same cancer type, such as breast or bowel. Each tumour has a genetic code that makes it unique, but there are also genetic differences within the tumours themselves. And tumours can evolve over time to become resistant to treatment.

To better guide treatment strategies, every cancer case has to be evaluated independently and monitored for changes over time. With recent advances in cancer genetics, we can better understand the difference between cancer and normal cells and pinpoint where things have gone wrong.

When cancer cells rupture and die, they release their contents, including their DNA with their unique genetic code, into the bloodstream. This free-floating DNA is referred to as circulating tumour DNA (ctDNA).

Through development of refined techniques to measure and sequence this ctDNA in the bloodstream, scientists can get a snapshot of the cancer itself, which is referred as a “liquid biopsy”. Taken over time, such blood samples would show clinicians whether treatments are working and whether tumours are developing resistance.

This is like evaluating changes in household diets by screening rubbish bins. This can be done repeatedly without disturbing the privacy of family.

Liquid biopsies

Classical methods for monitoring cancer dynamics, such as tumour markers and scans to estimate tumour size, can’t assess the tumour’s genomic status.

Genetic analyses of a sample of the tumour, also referred as a biopsy, are becoming standard care in pathology departments. However, a biopsy only provides a snapshot of genomic changes on that particular piece of tumour. A biopsy also commonly requires an invasive surgical procedure, so cannot be performed frequently.

So if changes are occurring over time, decisions based on old results will be outdated. Better methods to study tumour evolution can greatly improve cancer care.

One of the most advanced examples of liquid biopsy application in cancer care is in the treatment of lung cancer. Researchers discovered that around 60% of lung cancers treated with a drug to target something called the epidermal growth factor receptor (EGFR) on cancer cells, become resistant to therapy. Then they found the culprit responsible for the resistance: a small change in the EGFR gene, known as T790M mutation.

Scientists were then able to devise a new drug to target T790M. So when patients develop resistance to the first therapy, they could be treated with this new drug.

In parallel, development of a test to detect this mutation in blood plasma or even urine ctDNA, allows for patients to be monitored and timely change of treatment to occur when resistance starts to show.

Our recent study showed that response to treatment can be tracked by measuring ctDNA in the blood of melanoma patients. A decrease in the amount of ctDNA accurately mirrored the shrinking of the cancer. But more importantly, increases in ctDNA indicated that the cancer was coming back.

This is important as it can expedite treatment change when the cancer is still under control and the patient’s health hasn’t been compromised. We could also detect the development of mutations that the melanoma acquired in its genes to become resistant to treatment. This can inform treatment strategies as more drugs become available for metastatic melanoma.

Other developments

In addition to ctDNA, there is intensive research of other blood components that can reveal what is going on in a patients’s cancer. These components include cancer cells that released into circulation, called circulating tumour cells or CTCs, small droplets released by the cancer called exosomes, and other types of genetic material and proteins.

A team of researchers at the Walter and Eliza Hall Institute showed recently that colon cancer patients with detectable ctDNA in the blood after the tumour was removed by surgery, are at high risk of the cancer coming back. Using such a test will identify these high-risk cases so the residual cancer can be removed.

The promises of what we can discover about the patient’s tumour from a simple blood sample are still scratching the surface. As this window widens, a better and more complex picture of the cancer emerges, empowering researchers and clinicians with more information to deploy the anti-cancer arsenal at their disposal.

The Conversation

Elin Gray receives funding from the National Health and Medical Research Council. Elin is employed by Edith Cowan University to undertake research on cancer blood biomarkers.