For over 15 years, Dr Anthony Shum, a pulmonologist at the University of California, San Francisco has been studying a rare genetic disorder called the COPA Syndrome. It stands for coatomer subunit alpha and is a rare, inherited disorder that affects the lungs, joint, and kidney. The National Organization for Rare Disorder also notes that it is a genetic autoimmune disorder that is caused by mutations in the COPA gene. This disease affects families unpredictably—some individuals with the mutation develop severe lung damage early in life, while others remain completely healthy. Now, Shum’s team has discovered a protective genetic variant that may offer new hope for treatment.

A Breakthrough

Researchers found that some relatives of COPA Syndrome patients stayed healthy despite carrying the same COPA gene mutation that causes the disease. The key difference? These unaffected individuals had a protective version of another gene called HAQ-STING.

When scientists introduced HAQ-STING into diseased lung cells from COPA patients, the cells returned to a balanced state, suggesting that this gene could be used as a therapy.

“We really think HAQ-STING could be a gene therapy tool and a step toward a cure,” said Shum, whose findings were published in the Journal of Experimental Medicine.

Families Who Solved The Mystery

Shum’s journey into COPA Syndrome research began in 2011 when he treated a young woman, Letasha, who had severe lung bleeding. Her mother, Betty Towe, mentioned that Letasha’s sister, Kristina, had suffered from similar symptoms. Over the years, Betty had taken both daughters on a four-hour trip to UCSF for treatment. After tracing their family history, Shum discovered that their distant relatives in Texas and Oakland also had lung problems and arthritis. In 2015, Shum, along with scientists from Baylor College of Medicine and Texas Children’s Hospital identified the COPA gene mutation. They realized that it was the common factor behind the illness. However, only some of the 30 individuals with the mutation actually developed symptoms, leaving a major question unanswered.

The Domino Effect

It was established that it occurs when a mutated COPA gene causes another gene STING to go overdrive. The STING that helps fight infections in COPA patients, remain permanently active, which leads to chronic inflammation that damages the lungs, kidneys, and joints. In 2020, while studying STING’s role in the disease, researchers discovered a key variation: HAQ-STING. This version of STING, present in about one-third of the population, appeared to neutralize the harmful effects of the COPA mutation.

To confirm their theory, the scientists needed both affected and unaffected family members to participate in the testing. Letasha, Kristina and Betty immediately volunteered. The researchers then analyzed DNA samples from 26 COPA patients and their healthy relatives. They also conducted CT scans and blood tests to ensure that unaffected members did not have any hidden symptoms. When the findings were all clear, it was revealed that all the healthy individuals had HAQ-STING, while none of the COPA patients did. This was the first known case of a common gene variant completely protecting against a severe genetic disease.

Encouraged by this discovery, researchers tested HAQ-STING’s effects in a lab setting. They introduced it into diseased lung cells from COPA patients, and the cells returned to normal function.

Way Ahead

Shum believes HAQ-STING could lead to game-changing treatments, including:

• Prenatal gene therapy for babies diagnosed with COPA Syndrome before birth
• Aerosol delivery of HAQ-STING for adults, directly targeting the lungs

Before publishing their findings, Shum called Betty with the news—her own HAQ-STING gene had protected her from the disease. He also informed Letasha and Kristina, who were overwhelmed with relief and joy.

“We always believed Dr. Shum would get to the bottom of it,” said Letasha. “This discovery is going to change lives.”

Common metabolic conditions such as obesity and diabetes are increasingly becoming a serious public health concern in India. Their health implications extend beyond the conditions themselves, with obesity and diabetes associated with a range of chronic diseases and complications that can affect long-term health and wellbeing. As lifestyles become more sedentary and the prevalence of these conditions continues to rise, understanding their wider implications on women’s health is becoming increasingly important.

What many women may not realize is that this metabolic burden can carry a deeper, less visible consequence one that reaches into the domain of gynecological cancer.

One such concern is endometrial cancer. A form of uterine cancer, it develops in the lining of the uterus and is becoming an increasingly important health issue globally. Yet, many women remain unfamiliar with the disease, its risk factors, and the symptoms that require prompt medical attention.

The Metabolic Health Connection

Increasing evidence points to a link between metabolic syndrome and endometrial cancer, particularly through conditions such as obesity and diabetes. Excess body weight and metabolic disturbances can disrupt hormonal balance, such as by increasing estrogen production without a corresponding increase in progesterone. Over time, this hormonal imbalance may stimulate abnormal growth of the endometrial lining, increasing the likelihood of cancer development.

Diabetes, too, has been associated with an increased risk. As obesity and diabetes become more prevalent, recognizing these less-discussed consequences is an important part of strengthening women’s preventive health.

For women, maintaining a healthy weight, staying physically active, managing metabolic conditions effectively and paying attention to unusual symptoms can all form part of a broader approach to preventive health.

Watching Out For Unusual Symptoms

One of the most important characteristics of endometrial cancer is that it often presents with abnormal vaginal bleeding. Bleeding or spotting after menopause is one of the most significant warning signs and should never be ignored.

For women who have not reached menopause, heavier-than-normal periods, prolonged bleeding, or bleeding between periods should be discussed with a healthcare professional.

Why Awareness Matters

Improving awareness is important because there is currently no recommended routine screening test for endometrial cancer in asymptomatic women. As a result, recognizing symptoms and seeking timely medical advice are among the most effective ways to support earlier diagnosis.

At the same time, the conversation should not end with cancer awareness alone. As India continues to face a growing burden of obesity and diabetes, prioritizing metabolic health has become increasingly important for overall wellbeing.

Maintaining a healthy weight, staying physically active, eating a balanced diet, and effectively managing conditions such as diabetes can help reduce the risk of a range of serious health complications, including certain cancers. For women, understanding the connection between metabolic health and endometrial cancer can empower more informed decisions about prevention, symptom recognition, and long-term health. By addressing obesity and diabetes early and seeking medical advice when unusual symptoms arise, women can take meaningful steps towards protecting their health at every stage of life.

(By Dr. Shefali Sardana, Medical Oncologist, Apollo Hospitals, New Delhi)

Melanoma is often considered one of the more challenging cancers to treat, particularly when it has spread to distant organs. For early-stage disease, surgery remains an important treatment option. But once melanoma reaches stage IV, treatment becomes considerably more complex.

Understanding The Biology Of Advanced Melanoma

According to Dr. Mandeep Singh Malhotra, Cheif Mentor AOHC, cytotoxic chemotherapy has traditionally had a limited role in melanoma, while immunotherapy has changed the treatment landscape for many patients.

When melanoma is detected at an early stage and can be completely removed, surgery is generally considered the preferred treatment. Depending on the disease, this can involve removal of the primary tumour and assessment or treatment of regional lymph nodes.

But stage IV melanoma presents a very different challenge.

A Complex Case With Multiple Tumour Sites

Dr. Malhotra recalls the case of Sarah, who came to the team with multiple nodules in the scapular region. There were also lesions on both legs and a lesion in the pancreas. So there were multiple nodules. One in the right side of the leg, another in the left side of the leg. And there was a lesion in the pancreas.

Rather than relying on a standard treatment approach alone, the team first tried to understand the biology of the disease. As a standard protocol for this type of case, we first try to understand the disease biology. In Sarah’s case, the team used extensive testing, including chemosensitivity testing, transcriptomic analysis and next-generation sequencing.

Also read: Cancer Should Be Made Notifiable In India, Say Experts: Here’s Why

When Imaging Initially Suggests Progression

The results suggested sensitivity to certain drugs. When we analysed those reports, we were able to understand that cytotoxic drugs like temozolomide were effective. And checkpoint inhibitors like pembrolizumab, nivolumab were effective.

Based on these findings, the team developed a treatment protocol in which the main component was an immune checkpoint inhibitor along with low-dose temozolomide. Other agents, including lower doses of anti-VEGF, anti-FGF and CDK inhibitors, were also incorporated based on the analysis.

After around four weeks, the response became difficult to interpret on imaging. The PET scan suggested that all the lesions have had a pseudo progression.

Pseudo progression is a recognised phenomenon during immunotherapy. A tumour may appear larger initially because of immune-cell infiltration, even when the treatment is actually producing an anti-tumour response.

This is particularly relevant in melanoma treated with immune checkpoint inhibitors. However, doctors cannot simply assume that every apparent progression is pseudo-progression; true progression must also be considered and confirmed through Histopathology

Also read: French Court Links Flight Attendant’s Breast Cancer To Workplace Radiation; How Does Flying Increase Cancer Risk?

Histopathology Reveals A Dramatic Treatment Response

The team then proceeded with surgery, removing the nodules from the scapular region and both thighs. The specimens were sent for histopathological examination. And histopathology results were amazing. The tumours had gone necrotic.

The pathology showed extensive treatment-related changes, with inflammation and fibrosis around the nodules and only small areas containing viable melanoma cells.

Also read: _{Daraxonrasib: US FDA Approves Once-Daily Pill for Metastatic Pancreatic Cancer}

What Comes Next For The Patient?

For now, the plan is to continue the treatment for a few more cycles and then reassess the pancreatic lesion. The team is considering NanoKnife (irreversible electroporation) for the pancreatic lesion followed by Vaccines.

Certain cancer vaccines are being developed in certain labs in Germany and Europe and they are available for our patients in India on compassionate grounds. It's a very, very good response. And to achieve disease NED in stage four melanoma, I think we are really lucky and it's all due to the grace of God.

Why Individualised Treatment Matters In Stage IV Disease

The case also highlights an important point about advanced melanoma: treatment may need to be individualised according to the biology of the disease and the patient's response. At the same time, he stresses the need for hope. I hope that more people can benefit from this protocol and use this protocol to treat melanomas across the world.

For Sarah, the journey is still ongoing. The next step will be to reassess the pancreatic lesion and determine whether further local treatment can help achieve no evidence of disease (NED). A stage IV melanoma involving multiple sites, including the pancreas, reaching a point where NED may become a possibility is certainly an encouraging development. But it remains an individual clinical experience, rather than proof that the same protocol will work for every patient with metastatic melanoma.

By Dr. Mandeep Singh Malhotra, Director of Surgical Oncology at CK Birla Hospital and Chief Mentor at AOHC

People living with obesity and diabetes often feel healthy in their day-to-day life, but some of the most dangerous changes may be happening silently inside their bodies.

The liver is one of the first organs to be affected. In many cases, fat slowly accumulates in the liver without causing any pain, discomfort, or obvious symptoms. This is why fatty liver disease is often called a “silent condition.” By the time it is detected, it may already have progressed to an irreversible stage.

Excess body fat, particularly around the abdomen, disrupts how the body processes sugar and fats, placing continuous stress on the liver. Because of this silent progression, experts now strongly recommend that people living with obesity and type 2 diabetes should proactively check their liver health, even when they feel completely well.

Obesity is closely linked with liver damage through a series of metabolic changes that develop over time. When the body becomes resistant to insulin, fat begins to accumulate in liver cells, triggering inflammation and gradual injury.

If this continues unchecked, the condition can progress from simple fat accumulation to more serious stages, including metabolic dysfunction-associated steatohepatitis (MASH), where inflammation and liver cell damage become more significant.

Over time, this may lead to fibrosis (scarring of the liver), and in advanced cases, cirrhosis, which can severely affect liver function. Further, patients with fatty liver may directly present with liver cancer, which can occur in up to 20% of patients.

How Common Is Fatty Liver In People With Diabetes And Obesity?

In India, the burden of metabolic dysfunction-associated steatotic liver disease (MASLD) or fatty liver is rising and is now recognised as a common metabolic condition. Studies from the Indian subcontinent estimate that 1 in 3 people may have MASLD. Fatty liver is particularly common among individuals with metabolic risk factors.

It is seen in nearly 40–80% of people with type 2 diabetes and 30–90% of those with obesity, often without clear symptoms.iv Hospital-based trends also suggest increasing detection in younger age groups, reflecting changes in diet, reduced physical activity, and more sedentary lifestyles.

Also read: Post-Menopausal Women Face A Higher Risk Of Fatty Liver Disease: How Falling Estrogen Levels Impact Liver Health

What Liver Checks And Preventive Measures Should You Follow?

Preventive measures to be followed:

• If you live with excess weight/obesity and type 2 diabetes or PCOS (polycystic ovarian syndrome) or dyslipidemia, seek early consultation with a physician or hepatologist.

• Your doctor may request routine metabolic screening:

• Regular liver function tests as part of annual health check-ups

• Ultrasound screening for individuals with obesity or diabetes

• Monitoring blood sugar, cholesterol, and triglyceride levels

• Liver scarring scan (annually for patients with diabetes/obesity)

• Avoiding long-term neglect of “mild” or borderline test results

Also read: From Liver Inflammation to Cancer: When Hepatitis Becomes a Serious Warning Sign

With rising obesity rates in India, early liver screening should become a routine part of preventive healthcare. Even modest weight reduction, improved diet quality, and regular exercise (approximately 150 minutes per week of moderate-intensity exercise (example: brisk walking, gardening, swimming, cycling) or 75 minutes of vigorous exercise (example: weight training) can significantly reduce liver fat and inflammation within 3-6 months.

However, once the disease progresses to MASH or fibrosis, reversal becomes more difficult and may require long-term medical management. Early-stage fatty liver disease is reversible in many cases. In fact, medications can even reverse liver fibrosis (early scarring), but in only 25% of patients. Simple homemade food is sufficient to prevent these lifestyle diseases, and there is no need for “fancy online diets or supplements”.

Our forefathers lived longer by consuming homemade food and water without any supplements. Newly approved therapies such as semaglutide (GLP1 analogues) have been shown to resolve steatohepatitis and reduce liver fibrosis. These liver benefits do not appear to be explained solely by weight loss, suggesting a broader potential impact on liver health.

The absence of symptoms does not mean the absence of risk. Taking care of the liver early is not just about preventing disease; it is about protecting long-term health, energy, and quality of life.

By Dr. Anand V. Kulkarni, Senior Consultant Hepatologist & Director – Critical Care Hepatology, AIG Hospitals, Hyderabad