The class of drug known as p110δ inhibitors, currently being used to treat leukemia, has the unexpected side-effect of boosting immune responses against many different cancers, according to a study led by pharmaceutical company Genentech in San Francisco
p110δ inhibitors have shown such remarkable efficacy against certain leukemias in recent clinical trials that patients on the placebo were switched to the real drug - but they have not been tested in other types of cancer.
The p110δ enzyme is a member of the PI3-kinase family, and is sometimes called PI3Kδ. p110δ and the other PI3Ks are hot drug targets for the pharmaceutical industry as they are implicated in many cancers and are readily druggable.
A new study in Nature provides the first evidence that such drugs can significantly restrict tumor growth and spread and reduce the chances of relapse for a broad range of cancers. The researchers showed that inhibition of the p110δ enzyme helps to boost the body’s immune system to kill tumor cells.
Lead author Dr Khaled Ali, now based at Amgen, San Francisco, says, “When we first introduced tumors in p110δ-deficient mice, we expected them to grow faster because p110δ is important for the immune system. Instead, some tumors started shrinking. When we investigated this unexpected effect, we found that p110δ is especially important in so-called regulatory T cells which are suppressive immune cells that the tumors engage to protect themselves against immune attack.”
Mouse. Credit: UCL
“Our study shows that p110δ inhibitors have the potential to offer effective immunity to many types of cancer by unleashing the body’s own immune response,” says study co-leader Professor Bart Vanhaesebroeck of the UCL Cancer Institute, who first discovered the p110δ enzyme in 1997. “p110δ is highly expressed and important in white blood cells, called ‘leukocytes’. Given that leukemias are the result of leukocytes becoming cancerous, they are a natural target for p110δ inhibitors. Now, we have shown that blocking p110δ also has the remarkable effect of boosting the body’s immune response against leukemias as well as other cancers.”
The team showed that inhibiting p110δ in mice significantly increased cancer survival rates across a broad range of tumor types, both solid and hematological cancers. For example, mice in which p110δ was blocked survived breast cancer for almost twice as long as mice with active p110δ. Their cancers also spread significantly less, with far fewer and smaller tumors developing. Survival after surgical removal of primary breast cancer tumors was also vastly improved, which has important clinical implications for stopping breast cancer from returning following surgery. The team’s data further show that following p110δ inhibition, the immune system could develop an effective memory response to completely fight off the cancer.
“Our work shows that p110δ inhibitors can shift the balance from the cancer becoming immune to our body’s defences towards the body becoming immune to the cancer, by disabling regulatory T cells,” says study co-leader Dr Klaus Okkenhaug of the Babraham Institute. “This provides a rationale for using these drugs against both solid and blood cancers, possibly alongside cancer vaccines, cell therapies and other treatments that further promote tumour-specific immune responses.”
Professor Nic Jones, Cancer Research UK’s chief scientist and director of the Manchester Cancer Research Centre, said, “Treatments that train the immune system to recognise and kill cancer cells are showing huge promise in several types of cancer. This new finding, although only at an early stage, offers the potential to develop more treatments that can do this in many more cancers, including ones that have real need for more effective treatments such as pancreatic cancer.
“If the findings hold true in cancer patients this could make a big difference to many of them. The good news is that because the drugs used in this study are already being used in the clinic, we could see rapid translation of this research into patient benefit.
Source: University College London
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- Wait, Let's Not Be In Such A Rush To Go Multiplanetary Or Interstellar - A Comment On Elon Musk's Vision
- Petition To Youtube To Halt Ads On Doomsday Videos - They Make The Vulnerable Suicidal
- Paleo: In A Clinical Trial, Bread Made With Ancient Grains Could Benefit Heart Health
- Hubble Spots Europa Geysers Again - How They Did It - And What Next? Flyby? Lander?
- Why Psychology Lost Its Soul - Science Replaced It
- Chatelperronian Hominins: Disputed Neanderthal Region Confirmed In France
- No Go Area! What? What is that?
- "I don't think that much of the Kardashev scale. Especially L2,3 star vs galaxy. How would it be..."
- "When Descartes claimed ... the soul ... is eternal and indivisible... it's obvious he starts with..."
- "Oh, sorry to hear that, I hear this so often. Basically it's like propoganda I think. Propoganda..."
- "Hi mr walker... lately i havent been able to eat or drink.. and if i do sleep its during the whole..."
- "Right, California did, but prior to that there were schools in Marin with only 25% vaccination..."
- Is Parenting Kids of Human and Canine Persuasion the Same? Yes!
- Diabetes: MiniMed 670G Hybrid Closed-Loop Insulin System Is A Waypoint To An Artificial Pancreas
- Celebrate Oktoberfest with Beer Chemistry
- Littlest Consumers Doing Well, Nutrition-wise
- Herpes Vaccine Update: Exciting News, But Don't Throw Away Condoms Just Yet
- Ben & Jerry’s Asks Us to Take Big Lick of Fear & Hype
- Antipsychotic medications linked to increased risk of pneumonia in persons with Alzheimer's disease
- Multiple sclerosis misdiagnosis shows need for improved education of clinicians
- Brown adipose tissue can secrete factors that activate fat and carbohydrate metabolism
- Therapeutic Gene Delivery for Inherited Retinal Degeneration in Children
- Molecular atlas of the pancreas