Scientists map molecular steps in the development of endometrial cancer

A new study reveals the molecular steps that bring about endometrial cancer, commonly known as uterine cancer, which is the sixth most common cancer in women across the globe. The new insight will help doctors to better identify which patients may need aggressive treatment, and why conventional treatments may not be effective for some patients.

The study, funded by the National Cancer Institute and published in the journal Cell, provides a detailed look at dozens of molecular steps that happen in the development of this type of cancer. It is the most comprehensive molecular study of uterine cancer. It has defined how genes and proteins play significant roles in endometrial cancer, offering doctors the potential to provide individualized treatment approaches for patients.

The researchers from NYU Grossman School of Medicine and other institutions measure key proteins, which are workhorses that build molecular structures and signaling networks. They found that already-approved drugs that target proteins known as CDK12, PML, and SMARCA4 in other types of cancer may help in the treatment of endometrial cancer.

The new study from NYU Langone researchers provides an in-depth survey of the molecular players in endometrial cancer and suggests new treatment approaches. High and low power microscopic view of endometrium (uterus) to show endometrial cancer

More than genes

The new study built its work in The Cancer Gene Atlas (TCGA), which identified some of the genetic underpinnings of the disease in 2013. The scientists suggest that there is more to cancer than just genes.
 
To land to their findings, they analyzed 95 uterine tumors and 49 normal uterine tissue samples. With these, they measured the levels and modifications of molecular players, such as genes, microRNAs, circular RNAs, messenger RNAs, and proteins.

The team also studied the chemical changes to proteins, known as post-translational modifications, which is essential to determine when and where proteins are inactive or active. In a nutshell, the team collected 12 million measurements of differences between healthy cells and cancerous cells.

With the millions of measurements, the researchers developed a new method to determine tumors that are not aggressive now but will turn out to be as invasive as serous tumors, which are very potent and can kill patients.

At present, to determine how aggressive endometrial cancer is, doctors rely on biopsy or viewing the cells under a microscope. However, in the study, the team suggests that activity levels of some proteins can differentiate tumors that are more aggressive from less aggressive tumors.

Interestingly, the scientists also found that one process, which involved packing and unpacking genes, occurs more often than expected in cancer cells. Further, they found that a process called histone acetylation, which is a crucial part of the process, exists in endometrial cancer.

A promising avenue for treatment

The findings of the study allowed the researchers to devise a new way to determine which patients are most likely to benefit from a treatment called immune checkpoint therapy.

In the therapy, doctors use drugs like nivolumab and pembrolizumab to remove the barriers that most tumor cells use to escape the immune system. These immune checkpoint inhibitors fight cancer by blocking checkpoint proteins from binding with their partner proteins, preventing the turn off signal from being sent. Hence, the drugs allow the T cells of the immune system to kill cancer cells. It’s like boosting the power of the body’s immune system to fight cancer itself.

The new study now shows promise in treating patients who may need more aggressive treatment, reducing the risk of the tumor cells become invasive. Determining which patients would benefit from the drugs would help spare patients severe and unneeded side effects.

“For many years, scientists have been using genomics, the study of the genetic code, which is a very effective way but a relatively basic way to look at cancer. But if we add on all these extra levels--proteins, RNA, and the ways proteins talk to each other--then we can learn even more about how cancer is actually working,” Emily Kawaler, a student at NYU Grossman School of Medicine and study co-author, said.

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Researchers design home urine test for prostate cancer

Men will now be able to detect prostate cancer at home by just collecting their urine samples as researchers have developed a simple testing method.

Scientists pioneered the test which diagnoses aggressive prostate cancer and predicts whether patients will require treatment up to five years earlier than standard clinical methods.

Their latest study shows how the ‘PUR’ test (Prostate Urine Risk) could be performed on samples collected at home, so men don’t have to come into the clinic to provide a urine sample - or have to undergo an uncomfortable rectal examination.

This is an important step forward because the first urination of the day provides biomarker levels from the prostate that are much higher and more consistent. And the research team hopes that the introduction of the ‘At-Home Collection Kit’ could revolutionise the diagnosis of the disease.

“Prostate cancer is the most common cancer in men in the UK. It usually develops slowly and the majority of cancers will not require treatment in a man’s lifetime. However, doctors struggle to predict which tumours will become aggressive, making it hard to decide on treatment for many men,” said Lead researcher Dr Jeremy Clark, from UEA’s Norwich Medical School.

“The most commonly used tests for prostate cancer include blood tests, a physical examination known as a digital rectal examination (DRE), an MRI scan or a biopsy. We developed the PUR test, which looks at gene expression in urine samples and provides vital information about whether a cancer is aggressive or ‘low risk’, Clark continued.

“Because the prostate is constantly secreting, the collection of urine from men’s first urination of the day means that the biomarker levels from the prostate are much higher and more consistent, so this is a great improvement. Being able to simply provide a urine sample at home and post a sample off for analysis could really revolutionise the diagnosis,” Clark added.

“It means that men would not have to undergo a digital rectal examination, so it would be much less stressful and should result in a lot more patients being tested,” said Clark in the study published in - BioTechniques.

The research team provided 14 participants with an At Home Collection Kit, and instructions. They then compared the results of their home urine samples, taken first thing in the morning, with samples collected after a digital rectal examination.

“We found that the urine samples taken at home showed the biomarkers for prostate cancer much more clearly than after a rectal examination. And feedback from the participants showed that the at-home test was preferable,” revealed Clark.

“Using our At Home test could in future revolutionise how those on ‘active surveillance’ are monitored for disease progression, with men only having to visit the clinic for a positive urine result. This is in contrast to the current situation where men are recalled to the clinic every six to 12 months for painful and expensive biopsies,” continued Clark.

“Because the PUR test accurately predicts aggressive prostate cancer and predicts whether patients will require treatment up to five years earlier than standard clinical methods - it means that a negative test could enable men to only be retested every two to three years, relieving stress to the patient and reducing hospital workload,” added Clark. 

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Aggressive breast cancers more likely to hit black and younger women

Younger women face elevated risks of developing breast cancers that are not only aggressive but also less responsive to treatment, a new study confirms. 

Researchers found that non-Hispanic black women were more than twice as likely as white women to be diagnosed with so-called triple-negative breast cancers, while women under 40 were nearly twice as likely to be diagnosed with the aggressive cancer as those aged 50 to 64, according to the study. 

In their analysis of more than one million cases of breast cancer between 2010 and 2014, the researchers also found that triple-negative cancers occurred more rarely than had previously been reported. 

The researchers did not respond to requests for comment but did supply a press statement. “We hope that this update on the epidemiology of triple-negative breast cancer can provide a basis to further explore contributing factors in future research,”  a researcher said in the statement. 

Noting that few previous studies had looked beyond the scope of a single state, researchers turned to the U.S. Cancer Statistics database, a population-based surveillance system of cancer registries with data that represents 99% of the U.S. population. The researchers identified 1.15 million cases of breast cancer between 2010 and 2014 in women from 39 states, including 96,749 cases (8.4%) of triple-negative cancer. 

Analyzing the data, the team found that non-Hispanic black women were 2.27 times more likely to be diagnosed with triple-negative breast cancer than non-Hispanic white women. Women under 40 were 1.95 times more likely than women aged 50 to 64 to be diagnosed with the aggressive cancer. 

The researchers also found that when women were diagnosed with a late stage cancer, it was more likely to be triple-negative.

The study confirms what cancer specialists have been seeing, said  a medical oncologist. Some of the increased risk in younger women can be tied to the BRCA1 gene, the Dr. said. “Besides BRCA1, we don’t have a clear cause for it in these women,” he added. 

Dr. was struck by the size of the study. “This is one of the larger, if not the largest, so far,” said a professor of medicine.

Another striking thing is triple-negative breast cancer was thought to be 15% of the total but this study found it was 8.4%.

That change could be due to a tightening of the definition of triple-negative breast cancer, the Dr. said. 

According to the U.S. National Cancer Institute, triple-negative breast cancer cells do not have estrogen receptors, progesterone receptors, or large amounts of a protein called HER2/.

While this study and earlier ones showed that triple-negative breast cancer is more common in women under 40, “I hear all the time from younger women that they were initially told by a doctor that they were too young to have breast cancer, said a Dr. “Most of them were symptomatic. They had lumps or discharge. A lot of times I see women who had lumps for 18 months before I saw them.” 

Since younger women aren’t screened regularly, the Dr. advises them to “be vigilant. Know your breasts and what is normal. Make sure you have a relationship with a provider who trusts you and who will work with you.” 

There’s a lot of misinformation out there about triple-negative breast cancer, the Dr. said. “The message on the internet is that this disease is like death sentence,” he said. “It has a higher mortality rate than other breast cancers, but 65% to 70% of people go on to be cured with conventional therapy.”

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Tongue bacteria could help identify patients with early-stage pancreatic cancer

The different types of bacteria living on the tongue can distinguish patients with early pancreatic cancers from healthy individuals, according to results from a new study.

This is the first evidence that suggests changes to the bacteria in the tongue could be an early indicator of pancreatic cancer. If confirmed in larger studies, this could pave the way towards the development of new life-saving early detection or prevention tools for this highly aggressive disease.
Early diagnosis of pancreatic cancer can greatly improve chances of successful treatment – but this poses challenges for this disease as it grows deep inside the body and often shows few symptoms before it has already spread. As a result, most patients already have advanced disease by the time they seek medical help.

With researchers searching for biological changes that can accurately detect early signs of pancreatic cancer, a current hot topic is the potential role of the microbiome in the development of cancer. Previous studies have already seen dramatic disruptions to bacteria in saliva, intestinal and faecal samples collected from pancreatic cancer patients compared to healthy individuals.

In the first study to characterise the tongue coat microbiome of patients with pancreatic cancer, a team of researchers recruited a group of 30 patients with early-stage disease (diagnosed with a tumour positioned in the ‘head’ area of the pancreas) and a similar group of 25 healthy people.

Participants were all between 45 and 65 years in age, had no other diseases or oral health problems and had not taken any antibiotics or other drugs for the three months before the study.

The research team used gene sequencing technologies to examine the microbiome diversity of tongue coat samples and found that pancreatic cancer patients were colonised by remarkably different tongue coating microbiomes compared to healthy individuals.

Speaking about it, lead author said, “Although further confirmatory studies are needed, our results add to the growing evidence of an association between disruptions to the microbiome and pancreatic cancer.”

Notably, the abundance of four types of bacteria – low levels of Haemophilus and Porphyromonas and high levels of Leptotrichia and Fusobacterium – could distinguish pancreatic cancer patients from healthy individuals.

The research team hypothesises that the immune system is most likely a link between any confirmed shifts in the microbiome with pancreatic cancer. They theorise that disease development in the pancreas may influence the immune response in ways that favour the growth of certain bacteria – or vice versa. If proven, this could set the stage for the development of new treatment strategies involving antibiotics or immunotherapies – or potentially even probiotics that can help prevent pancreatic cancer in high-risk patients in the future.

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Obesity May Up Risk Of Cancer In Teens

Does your 13 year old weigh much more than his BMI? Is he/she always surrounded by fattening and sugary foods? It is time you do something about the condition, or he/she might be at a risk of  developing cancer. According to a latest study, obesity increases risk of 13 different cancers in young adults.The study published recently, demonstrated how obesity may shift certain cancers to younger age groups, and intensify cellular mechanisms promoting the disease.

Cancer's increasing frequency in young adults has taken the entire medical circuit by storm. Earlier the disease was associated with people in their 50's.

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The new meta-analyses integrates animal studies, clinical trials, and public health data to help explain rising cancer rates among young adults.

Explaining how the childhood obesity "pandemic" promotes cancer, the study also offered approaches to better track the health crisis, and hopefully avert the risk.

Obesity is a disorder characterized by excessive body fat that increases the risk of health problems. Young people with body mass indexes (BMIs) over 30 are more likely to experience aggressive malignancies, noted the authors of the study.

The risk of cancer may remain even after the weight loss. The greater the body weight, the greater is the risk of cancer. It may alter a person's DNA, that may add up with time, which may even stay long after weight loss. If you lose weight, it improves the prognosis and may lower your risk, but it never goes away completely, noted the researchers.

The state of obesity is closely linked to stages of cancer progression. According to the researchers, obesity triggers the immune system in such a way, that they produce harmful byproducts like peroxide and oxygen radicals that mutate DNA.

Obesity can also take a direct toll on your metabolism. It can alter it in a way, causing growth factor and hormone imbalances that help cancer cells to grow and multiply.

The changes in the gut flora, could be severely affected by obesity too. These changes may facilitate tumor-promoting species to thrive.

The scientists also explained how acid reflux in obese individuals may damage swallowing tubes and elevate the risk of esophageal cancer.

The researchers said, even if one is successful in blocking one pathway, the obesity- induced cancer takes another path, and the trigger multiple other risks.

One of the studies that were part of the meta-analysis was conducted on 1.1 million Israeli men who were tracked over time. Those who were overweight in adolescence (age 16-19) had a 1.5-fold increased risk of developing colon cancer by age 48.

The researchers reinforced the idea of documenting health data, including BMI, throughout a patient's life. Doctors are advised to always scan for the history of obesity. Many cancer patients present after significant weight loss, which could cause doctors to overlook obesity-related factors.

Electronic medical records may help build databases that can detect weight loss patterns, the researcher suggested. About, 110 million children and adolescents with obesity worldwide remain at risk of developing obesity-associated cancers. A comprehensive data tracking the weight gain and weight of these children are a need of the hour.

From children to adults, obesity sees no age and can affect anybody. Re-organising your kitchen, swapping the fat-laden unhealthy junk with nutrient-dense food is the best gift you can give to yourself. Swap refined carb sources for whole grains. Whole grain manages to retain all the nutrients that are processed in the refining. Stock up on whole grains like bajra, ragi, maize and jowar and use them often. Try red, black and brown rice instead of white rice .You can use these whole grains for breakfast porridge. Just like grains, whole dals are also a better bet than the washed dals. Rajma, and chana dals are some of the healthiest dals you can fill up your shelves with. You can cook them, have them in sprouts or in soups. Avoid red meat and opt for lean meat like chicken and salmon. Adding protein with every meal could prove to be a game changer for anyone trying to lose weight. Load up on seasonal vegetables. They provide both soluble and insoluble fibres in addition to vitamins, minerals and antioxidants.

Starving is not a sustainable way to lose weight. A balanced and healthy diet can help one manage obesity better.