A breakthrough in lung cancer treatment and gene therapy to reverse deafness
Hello!
It’s been a week that’s felt more like a year. Results of elections in India were declared and yesterday India beat Pakistan in the T20 World Cup match that turned out to be a nail biter in New York. Naturally, I’m jealous of everyone who was able to go to the match and see it in person, but it’s good to see India start off well, and the local side U.S.A. start off respectably.
If you’re still hungover from election news, I have a strong morning broth of science news that you probably missed. Fear not, I bring good news.
A breakthrough in lung cancer treatment
I’ve been interested in lung cancer treatments for a few decades now. Close to fifteen years ago, I wrote an editorial for a science journal straight from a meeting on a revolutionary treatment (at the time) for this serious disease.
My interest isn’t strictly scientific, it is personal. My grandmother succumbed to lung cancer in her seventies.
I’m pleased to say that cancer treatments have improved dramatically in the last two decades.
A few days ago, at the American Society of Clinical Oncology meeting, breakthrough results were released that could change the landscape of lung cancer treatment. These findings bring new hope to a disease responsible for more deaths worldwide than any other cancer, often detected too late to treat effectively.
In India, lung cancer is a major health issue due to limited access to treatments and high exposure to risk factors like smoking and pollution.
Lung cancer rates are rising, especially in urban and northeastern areas, mainly because of higher smoking rates and significant air pollution.
Second-hand smoke from cigarettes and bidis also increases lung cancer risk. While policies banning public smoking have helped reduce exposure, enforcement remains inconsistent.
Beyond smoking, India faces risks from smokeless tobacco and the use of biomass fuels for cooking in rural areas, which release carcinogenic pollutants.
Smokers are about 20 times more likely to develop lung cancer than non-smokers. However, non-smokers can also get lung cancer due to genetic factors and environmental issues like air pollution.
(My grandmother was not a smoker, but she consumed paan with tobacco).
Cancer is caused by genetic mutations leading to uncontrolled cell growth. Lung cancer is particularly challenging because of its genetic complexity and its tendency to spread to the brain. It includes small-cell and non-small-cell types, with non-small-cell lung cancer being the most common, making up about 85% of cases.
One type of non-small-cell lung cancer involves mutations in the anaplastic lymphoma kinase gene, leading to cancer growth. Traditional treatments like chemotherapy and radiation are often ineffective for advanced stages. This type of cancer frequently affects younger, non-smoking patients and is particularly deadly due to its spread to the brain.
About a quarter of patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer develop brain metastasis within two years. This has driven the search for more targeted treatments.
Lorlatinib, a targeted therapy available in India, inhibits the anaplastic lymphoma kinase protein's activity, which promotes cancer cell growth. It can cross the blood-brain barrier, allowing it to treat brain metastases effectively.
The study led by Dr. Benjamin Solomon, presented at the American Society of Clinical Oncology meeting and published in the Journal of Clinical Oncology, showed promising results. Nearly 300 patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer were treated with lorlatinib or crizotinib. After five years, over half the patients on lorlatinib had no cancer progression.
Lorlatinib is now the best-performing single treatment for advanced non-small-cell lung cancer and metastatic solid tumors.
It’s a small study focusing on one subset of patients with one kind of cancer, but it is indicative of a broader trend in cancer treatment.
Targeted therapies like lorlatinib focus on specific genetic changes, offering hope for longer survival and better quality of life.
Gene therapy allows children to hear for the first time
For a set of children, gene therapy has enabled them to hear for the first time in their lives.
For most of us, hearing a loved one’s voice or listening to music is taken for granted. But for five children in China born deaf, this is now a reality thanks to groundbreaking gene therapy reported in Nature Medicine on June 5. This treatment delivered a working copy of a crucial gene to their inner ears, allowing them to hear.
Hearing loss affects over 430 million people worldwide, including 34 million children. Approximately 26 million people are born with hearing loss, with 60 percent of cases due to genetic factors. One such factor is autosomal recessive deafness 9 (DFNB9), caused by a mutation leading to a faulty otoferlin protein, affecting 2-8 percent of children born deaf globally.
Otoferlin is essential for hair cells in the ear to detect sound and send signals to the brain. Without this protein, children with DFNB9 experience hearing loss from birth. The five children in the gene therapy trial, aged 1 to 11, were all born with DFNB9 and could not hear.
The gene therapy uses engineered viruses to carry the working otoferlin gene into the inner ear's hair cells. Because the otoferlin gene is too big for a single virus, it’s split into two parts and delivered using two separate viruses in one surgery. Inside the cells, the parts combine, making the gene work properly.
In an earlier trial, researchers restored hearing in one ear of other deaf children. The latest trial treated both ears of the five children, helping them hear more evenly and effectively.
Six months after receiving the therapy, the children's hearing improved greatly. They showed great improvements in understanding speech and locating sounds, aiding them in noisy places, enjoying music, and detecting warning signals.
Encouraged by these results, researchers plan to treat the second ear of the children from the first trial. This effort is part of a larger initiative to expand gene therapy for hereditary deafness worldwide. Similar trials in other countries could lead to treatments for other genetic forms of deafness.
Early detection of genetic causes through newborn screening and better genetic test interpretations are crucial. Different genetic mutations will need different treatments, and methods for regenerating sensory cells will be needed.
The progress so far is fantastic. This breakthrough brings us closer to a future where a world of sound is unlocked for many more people.
Thanks to everyone who has already shared their comments on When The Drugs Don’t Work. I love hearing from you.
Last week, I thoroughly enjoyed the book chat with IndiaBioscience. My thanks to Dr. Karishma Kaushik for being such a gracious chat host.
If you missed the discussion, you can still catch it below.
That’s it for now!