Thursday, February 03, 2022

World Cancer Day: Prevention and early detection is key to tackling cancer

It is estimated that India could witness more than 1,00,000 cancer-related death in the next five years, as reported by Lancet Study. However, as per WHO cancer mortality is significantly reduced when cases are detected and treated early. Surprisingly, two-thirds of the cancer cases are usually diagnosed when the disease reaches an advanced stage, thereby reducing the chances of a patient’s survival. Cancer prognosis can depend greatly on the stage of cancer, with terminal cancer being one that cannot be cured or treated. Therefore, by adopting prevention, early detection including early diagnosis, and screening programs, patients have hugely increased the chances of successful treatment and longevity.

Cancer diagnosis is the beginning of the journey to unlock your chances of survival and eliminate the disease- critical to this is to provide people with the knowledge, skills, and confidence – as well as the opportunities – to close the healthcare gap and ensure universal health access and coverage.

Understanding and recognizing the inequities in cancer care

Inequalities in health are probably one of the most convincing measures which represent the vast inequalities of our society. Estimates by Global Cancer Statistics summarize that cancer is a major cause of death across the world, second only to cardiovascular diseases. Cancer indicators and their incidence patterns are further proof. A closer look at incidence rates through socio-economic, racial, and ethnic groups reveals significant differences. Research conducted by Lancet says that a number of patients from lower-income groups are diagnosed with the late-stage disease for cancers that are potentially detectable at an early stage through screening. But efforts are underway in the scientific, medical, economic, and policy arenas such as implementation of schemes like Ayushman Bharat, National Health Mission programme, National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS), Tertiary Care Cancer Centers (TCCC) to further strengthen infrastructure, human resource development, health promotion, early diagnosis, management, and referral. This is likely to have a positive impact on the availability and effectiveness of interventions available for care, and the quality of life of cancer patients.

Challenging assumptions: A look at the facts

The problem with today’s fast-paced world is that much of the information available is sometimes inaccurate, or at worst dangerously misleading. There are plenty of evidence-based, easy-to-understand resources, reports, books, podcasts, interviews, expert opinions on cancer, but there are just as many, baseless assumptions that also exist. For a common man, it can be hard to distinguish fact from fiction, as most of this inaccurate information sounds believable.

False claims on the internet that cancer is a death sentence are not true. In fact, despite the sobering statistics, cancer is not always terminal. As scientists understand cancer better and develop improved treatments, recovery rates continue to improve. People also believe that cancer runs in families, although some cancers are passed on genetically through families, they represent a minority of such cases: an estimated 3–10% of cancers result from mutations inherited from parents.

Reducing stigma; listening to the various new forms of treatments and diagnosis available

Communication is the key to reducing stigma around cancer by raising awareness and promoting cancer education.

Researchers across the world have made major advances in learning more complex details about how to prevent, diagnose, treat, and survive cancer. At the forefront of emerging cancer research is the success of immunotherapy, the growing role of precision medicine, the influence that reducing health disparities can have on cancer outcomes, the use of new liquid biopsies, and machine learning, which is allowing scientists to make use of “big data”.

Precision medicine today is helping in cancer treatment where doctors can choose treatments that are most likely to successfully treat a person’s cancer based on the detailed genetic information of that person’s specific cancer. Advancements leading to faster and less expensive methods of gene sequencing, precision medicine is starting to be used more often to treat patients, most notably in the treatment of lung cancer.

A preventive approach is the best approach

Cancer screening is a significant part of overall cancer healthcare. One of the most effective ways to combat this disease is to detect it at an early stage and completely eliminate it from the body before the cancerous cells spread. Hence, the more frequently one is screened, the healthier and more protected they will be, resulting in improved health outcomes that matter to the patient, not simply to discover a disease state. The earliest the detection of the presence of cancer, the better survival rates are while also bringing with it a lesser amount of treatment in terms of both costs and use of radiation therapy.

Today there are technologically advanced Genetic testing options, mostly done through saliva or blood samples, also play a major role in the prevention of cancer as it contributes to personalizing the health aspect for an individual thereby reducing the curative costs of dreaded diseases like cancer. Inheriting a gene linked to cancer from either of the parents makes the individual much more likely to develop cancer and hence, they should opt for personalized genetic testing. These tests start from Rs 3000 and above depending on the nature and complexity of the test. Although only 5–10% of all cancer cases can be attributed to genetic defects, most cancers have their roots in the environment and lifestyle factors including tobacco consumption, diet, alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. Therefore, the only solution is full-scale defense through early detection and making lifestyle changes, so that nobody suffers in the first place.

Conclusion

Although the roadmap for early detection and diagnosis focuses on cancer, the future of health care lies not only in the effective treatment of symptomatic disease but also in health maintenance—i.e., a holistic, proactive approach to understanding disease risk, early detection of deviations away from health, and intervening appropriately, whatever the disease. Cancer acts as an example to establish technologies and approaches that will deliver benefit across a range of disease areas, incorporating disease prevention via interception of pre-disease, further underscoring the need for partnerships across the health network. With emerging technological capabilities and increased urgency in the post-COVID-19 era, an unprecedented opportunity exists to transform health outcomes.

 

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Friday, January 24, 2020

Research paves the way to improved treatment for complex blood disorders

Nearly 1.6 billion people worldwide suffer from anemia, and for the first time new research points to how resistance emerges to the drug dexamethasone used to treat the devastating inherited form of anemia known as Diamond Blackfan anemia (DBA). The Feinstein Institutes for Medical Research professor and expert in disorders of the red cell Lionel Blanc, PhD, published his conclusions today in the Journal of Clinical Investigation (JCI).

Research paves the way to improved treatment for complex blood disorders.

These findings are the first to be published that stem from a five-year, $2.5 million National Institutes of Health (NIH) grant Dr. Blanc received in 2019 to research improved treatment for erythropoietic disorders, including DBA. This rare type of anemia that is caused when bone marrow cannot make enough red blood cells and is typically diagnosed when a child is less than a year old.

Dr. Blanc analyzed the effects of dexamethasone, a corticosteroid used to treat inflammation, on red blood cell formation. The results revealed unique insights, including the identification of dexamethasone targets previously unrecognized in humans that show how it influences the cell cycle and red blood cell formation. The research was done in collaboration with investigators from Stanford University and New York Blood Center.

Because many patients who live with anemia are not responsive or cannot continue glucocorticoid treatment due to adverse side effects, the identification of these molecular targets could lead to the development of new drugs and treatment strategies for DBA and perhaps other forms of anemia.

Anemia, and specifically Diamond Blackfan anemia, are debilitating conditions. We are encouraged that the insights resulting from this work may lead to more effective therapies to treat these blood disorders. Through our research, we have also opened up new avenues for investigation of how DBA may also be linked to cancer.”     Dr. Lionel Blanc, Feinstein Institutes for Medical Research professor.


Because other tissues appear to behave in a manner similar to the developing red cell, these may reveal mechanisms relevant to cancer, especially in pediatrics. Thus through the analysis of both normal physiological as well as pathological human blood cell formation, Dr. Blanc hopes to investigate the development of cancer not just in developing blood cells but in broader cell populations.

Dr. Blanc is a recognized leader in hematology research. Before receiving NIH funding, he was awarded a five-year $550,000 career development grant from The St. Baldrick's Foundation, a not-for-profit organization to raise funds to help find cures for children with cancer.

Dr. Blanc was recently named the Les Nelkin Professor of Pediatric Oncology at the Zucker School of Medicine at Hofstra/Northwell.      

    Dr. Blanc’s leadership in discovering basic molecular mechanisms of anemia points the way to new therapies. His translational research lays the basis for finding new cures for complex blood disorders.”    Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes.


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Researchers discover 102 genes associated with autism

In the largest genetic sequencing study of autism spectrum disorder (ASD) to date, researchers have identified 102 genes associated with risk for autism.

The discovery shows significant progress towards teasing apart the genes associated with autism from those associated with intellectual disability and developmental delay, conditions which often overlap.

According to the World Health Organisation (WHO), one in 160 children has an autism spectrum disorder (ASD).

ASDs begin in childhood and tend to persist into adolescence and adulthood. In most cases the conditions are apparent during the first five years of life.

"This is a landmark study, both for its size and for the large international collaborative effort it required.

"With these identified genes we can begin to understand what brain changes underlie ASD and begin to consider novel treatment approaches," said Joseph D Buxbaum, Director of the Seaver Autism Center for Research and Treatment at Icahn School of Medicine at Mount Sinai.

For the study published in the journal Cell, an international team of researchers from more than 50 sites collected and analyzed more than 35,000 participant samples, including nearly 12,000 with ASD, the largest autism sequencing cohort to date.

Using an enhanced analytic framework to integrate both rare, inherited genetic mutations and those occurring spontaneously when the egg or sperm are formed, researchers identified the 102 genes associated with ASD risk.

Of those genes, 49 were also associated with other developmental delays.

The larger sample size of this study enabled the research team to increase the number of genes associated with ASD from 65 in 2015 to 102 today.

In addition to identifying subsets of the 102 ASD-associated genes, the researchers showed that ASD genes impact brain development or function and that both types of disruptions can result in autism.

"Through our genetic analyses, we discovered that it's not just one major class of cells implicated in autism, but rather that many disruptions in brain development and in neuronal function can lead to autism," said Buxbaum.

It's critically important that families of children with and without autism participate in genetic studies because genetic discoveries are the primary means to understanding the molecular, cellular, and systems-level underpinnings of autism.

"We now have specific, powerful tools that help us understand those underpinnings, and new drugs will be developed based on our newfound understanding of the molecular bases of autism," the researchers noted.

 

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Thursday, January 16, 2020

Scientists identify 'modifier gene' that determines severity of inherited kidney disease

Scientists have developed a new way to understand complex genetic diseases and have identified a gene that modifies the severity of inherited kidney disease, paving the way for personalised treatments.

Experts at Newcastle University, UK, have shown that the rate of kidney disease in people with Joubert syndrome is determined by the genetic makeup of the individual and each patient may respond differently to treatment.

Joubert syndrome is a complex disorder, affecting approximately one in 80,000 newborns, causing varying degrees of physical, mental and sometimes visual impairments. It is often associated with severe kidney disease that requires dialysis and ultimately transplantation.

The study, published online in the Proceedings of the National Academy of Sciences, is the first time that an explanation has been given for the difference of disease progression in Joubert syndrome patients.


Significant breakthrough

The Newcastle research has identified a second gene called BSND - a 'modifier gene' - which determines the severity of kidney disease in patients with CEP290 mutations of Joubert syndrome.

It has been assumed that these modifier genes exist, but they have never been found before in rare genetic conditions until now.

Professor John Sayer and Dr Colin Miles, from the Translational and Clinical Research Institute, Newcastle University, led the Medical Research Council-funded research.

Professor Sayer said: "We have shown, using mouse and human DNA samples, that BSND is a modifier gene for the severity of kidney disease in Joubert syndrome.

"This is the first time that a modifier gene for inherited kidney disease has been identified, and this information will improve diagnoses and will be used to develop therapies to reduce the severity of kidney disease in affected patients.

"Our research is a major step forwards and, in the future, we may be able to offer a therapy that switches on the protective modifier gene and reduces the development of genetic kidney disease.

"This work paves the way towards personalised therapies in patients with the inherited kidney disease."

The international study used mouse models and DNA samples from patients with Joubert syndrome to progress the research.

Scientists used mouse models of disease and genetic manipulation to see how the kidney disease responded to modifier gene manipulation, cross-referenced with DNA sequencing data from patients around the world to prove the modifier gene was relevant in humans.


Challenging disease
Professor Sayer, a Consultant Nephrologist at Newcastle Hospitals NHS Foundation Trust, said: "The treatment of genetic kidney disease is challenging, as this requires both the correction of the underlying gene defect and the delivery of the treatment.

"We have shown that the kidney disease in a mouse can be dramatically changed by switching on or off a modifier gene.

"This will mean that we can use this information to carry out treatments, including genetic therapies, to lessen the effects of inherited kidney diseases, such as Joubert syndrome.

"We are testing these treatments further in our model systems before we move into patient studies."

Within the next three years, research will start to test treatment of patients with modifier genes in the hope of developing personalised treatment plans.
Patient story

Siblings Emma, 11, and Ben Buckley, eight, have Joubert syndrome and both developed kidney failure before the age of eight.

They were diagnosed with Joubert syndrome from a few months of age and both have required dialysis and a kidney transplant.

They suffer from a range of medical issues due to Joubert syndrome, including visual impairment, communication problems and developmental delay.

The two children, of Whitley Bay, North Tyneside, have been instrumental in helping further the research over the years, allowing the Newcastle scientists to study the mutation in detail.

Parents Leanne and Michael say they welcome the findings of the Newcastle University-led study as it will help to give patients a chance of preventing kidney failure in the future.

Leanne said: "It is very important that research is done into Joubert syndrome and the linked kidney damage, as this will hopefully prevent patients in the future needing a kidney transplant.

"All throughout Ben and Emma's lives, they have lived with the effects of Joubert syndrome and scientists found they had a problem with the CEP290 gene.

"Both Ben and Emma have needed dialysis and kidney transplants because of their kidney problems and I would like to hope this research will help prevent kidney failure for other affected children.

"We were happy for Ben and Emma to provide samples for the study as anything that helps further understanding into the condition is well worth doing, so it's great to see the study's positive results."



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