WEILL CORNELL SCIENTISTS REVEAL HOW THE PROTEIN WORKS AND HOW THE DRUG GUMS IT UP, OFFERING NEW HOPE FOR TREATMENT OF AGGRESSIVE CANCER
Researchers have discovered how an experimental drug is capable of completely eradicating human lymphoma in mice after just five doses. The study, led by researchers at Weill Cornell Medical College, sets the stage for testing the drug in clinical trials of diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, itself the seventh most frequently diagnosed cancer in the U.S.
In the journal Cell Reports, published today online, the scientists describe how the powerful master regulatory transcription factor Bcl6 regulates the genome, ensuring that aggressive lymphomas survive and thrive. They also show how the Bcl6 inhibitor, developed at Weill Cornell, effectively gums up the protein, stopping it from working.
While Bcl6 is active in a number of cancers, including leukemia and breast cancer, work testing a Bcl6 inhibitor is most advanced in DLBCL. “That’s because we desperately need a new strategy to treat this lymphoma — many patients are resistant to currently available treatments,” says the study’s senior investigator, Dr. Ari Melnick, Gebroe Family Professor of Hematology/Oncology and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell.
Dr. Melnick developed the first BCL6 inhibitors nine years ago, and has continued to improve upon the design of these drugs so they could be used to treat cancer patients. He has since collaborated with colleagues at many institutions in a systemic effort to understand how both Bcl6 and its inhibitor drugs function.
In a study published in March in Nature Immunology, Dr. Melnick and his team reported that it is possible to shut down Bcl6 in DLBCL without affecting its vital role in the T cells and macrophages needed to support a healthy immune system. The protein has long been considered too complex to target with a drug as it also is crucial to proper function of many immune system cells, not just B cells gone bad.
That finding suggested Bcl6 inhibiting drugs may have few side effects, says Dr. Melnick, who is also a hematologist-oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
The latest study was designed to understand exactly how Bcl6 promotes DLBCL.
Transcription factors are responsible for either inhibiting or promoting the expression of genes, and master regulatory transcription factors are like transcription factors on steroids: their actions regulate thousands of genes in different kinds of cells. Bcl6 can control the type of immune cell that develops in the bone marrow — pushing them to become B cells, T cells, or macrophages — and it has a primary role in the developmental phase of B cells, during which they generate specific antibodies against pathogens.
The researchers found that in order to help B cells produce antibodies against an infection, Bcl6 “builds a huge shopping mall-style complex” that sits on top of a stretch of the genome. By binding onto these genes, Bcl6 deactivates the DNA, stopping genes from producing RNA and proteins. “Bcl6 acts like a barcode reader. When it sees that barcode — the DNA sequence — it attaches there,” Dr. Melnick.
Normally, the protein complex goes away after an immune reaction has been successfully mounted against the pathogen. But when it doesn’t, and remains stuck to the genes, DLBCL can result. That’s because Bcl6 is inhibiting genes that stop cells from dividing and that sense damage to the genome, Dr. Melnick says. “We now know the genes that Bcl6 is repressing and how that helps lymphoma develop and survive.”
Bcl6 also has a second, independent function that Dr. Melnick says acts like a switch on railroad track that routes a train in one direction or another. One track is needed when antibodies are required for an immune response, while the other keeps B cells in a constant state of division.
The researchers found that in order for DLBCL to survive, Bcl6 needs to maintain both its shopping mall protein complex and keep the train tracks on the path toward B cell division.
To their surprise, they also found that both the complex and the train switch attach to the Bcl6 protein at the same site. “They fit into the same keyholes on Bcl6,” Dr. Melnick says. “There are two identical binding sites on the protein surface.”
Even better, the Bcl6 inhibitor they developed was designed to fit into that same keyhole.
“This is wonderfully serendipitous — our drug just happens to be able to overcome both of the biological mechanisms that are key to survival of aggressive lymphoma,” Dr. Melnick says, adding that the inhibitor completely eradicated DLBCL in mice in a short time, with no detectable side effects.
The Latest Bing News on:
Lymphoma
- ADC Therapeutics Posts Early Phase II Lymphoma Data for Zynlonta as Revenue Drops 5.8%on May 7, 2024 at 6:17 am
ADC Therapeutics is positioning Zynlonta for a label expansion with new Phase II data showing that the treatment can elicit high rates of complete response in patients with relapsed or refractory ...
- Caring Cross and ImmunoAdoptive Cell Therapy (ImmunoACT) Announce Agreement to Commercialize TriCAR-T Cell Immunotherapy for Leukemia and Lymphomaon May 7, 2024 at 1:00 am
Agreement allows ImmunoACT to develop and commercialize a novel TriCAR-T cell therapy for leukemia and lymphoma designed to decrease lapses seen in current single CAR-T cell therapies and improve ...
- How you can give back to the Leukemia & Lymphoma Society this weekendon May 6, 2024 at 3:49 pm
MADERA, Calif. (KFSN) -- This weekend, you have a chance to round up your friends and give back to the Leukemia & Lymphoma Society. The mission of LLS is to help find cures for various types of cancer ...
- EXCLUSIVE: A wife noticed her husband’s eye looked smaller. It was a sign of a rare canceron May 6, 2024 at 9:52 am
Jennifer Cunningham, a nurse, saw that her husband's eye looked smaller. Eventually, he decided to see a doctor. He had a rare lymphoma in his eye socket.
- A third of patients with aggressive lymphoma face relapse or death, new drugs offer hope: Studyon May 5, 2024 at 7:09 am
New, effective cancer treatments approved for use in Singapore; hope for patients at risk of relapsing. Read more at straitstimes.com.
- Jeff Bridges Shares Health Update 3 Years After Lymphoma Diagnosis; Know All About The Conditionon May 3, 2024 at 3:56 am
Discover Jeff Bridges inspiring cancer journey and his message of hope and resilience in the face of adversity ...
- Calquence Regimen Improves Outcomes in Frontline Mantle Cell Lymphomaon May 2, 2024 at 1:59 pm
Adding Calquence to standard-of-care chemoimmunotherapy improved progression-free survival in patients with previously untreated mantle cell lymphoma.
- Global $11 Billion Non-Hodgkin Lymphoma Market Outlook, 2024-2029: Focus on T-cell Lymphoma and Immunotherapieson May 1, 2024 at 2:53 am
The global Non-Hodgkin Lymphoma market has experienced significant growth, with estimates indicating a surge from USD 7.14 billion in 2023 to USD 11 billion by 2029, showcasing a robust CAGR of 7.55%.
- Orlando Pride midfielder Luana out for season with Hodgkin’s lymphomaon April 29, 2024 at 2:58 pm
Pride midfielder Luana has been diagnosed with Hodgkin’s lymphoma, the club and Brazilian international announced on Monday. She immediately will begin chemotherapy treatment with Orlando Health ...
- Orlando Pride midfielder Luana diagnosed with Hodgkin's lymphomaon April 29, 2024 at 7:51 am
Orlando Pride midfielder Luana has been diagnosed with Hodgkin's lymphoma, the club announced Monday, saying the Brazil international is set to begin chemotherapy treatment immediately.
The Latest Google Headlines on:
Lymphoma
[google_news title=”” keyword=”Lymphoma” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
The Latest Bing News on:
TREATMENT OF AGGRESSIVE CANCER
- Anixa Biosciences Expands Partnership with Cleveland Clinic to Develop Additional Cancer Vaccineson May 8, 2024 at 5:24 am
Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a clinical-stage biotechnology company focused on the treatment and prevention of cancer, today announced that it has entered into a ...
- Video Shows Immune System Fighting Cancer, and It's Amazing to Watchon May 8, 2024 at 4:00 am
In a cancer-conscious world like ours, a new video circling the internet should bring some joy. A recent video has surfaced capturing the moment the immune system confronts and conquers a cancer cell.
- New blood cancer treatment on offer for Nottingham patientson May 7, 2024 at 10:17 pm
Lymphoma - one of more than 40 types of blood cancer - develops when white blood cells called lymphocytes grow out of control, and DLBCL is often an aggressive form of the ... Hospitals NHS Trust, ...
- New diagnostic and treatment approach could revolutionize bladder cancer careon May 7, 2024 at 10:27 am
A new diagnostic and treatment approach for bladder cancer will undergo a clinical trial in Queensland.
- Could cannabis treat cancer someday? Here's what the science says so faron May 7, 2024 at 9:03 am
For decades, cannabis has been studied for its potential antitumor properties, but whether it can actually treat cancer is still unknown.
- 'Younger patients tend to have more aggressive cancer': Breast cancer screening guidelines changeon May 6, 2024 at 3:25 pm
The U.S Preventative Services Task Force has lowered their age recommendation for women to get mammograms from 50 to 40.
- The New Frontier: How Smartphone Data Can Revolutionize Cancer Careon May 6, 2024 at 12:33 pm
Patient-generated "passive data," collected from smartphones, offers an alternative – continuous, real-time insights into the health and behavior of those living with ...
- Canadian influencer Sarah DeMelo opens up about 'aggressive, relentless rare cancer' one year after diagnosison May 6, 2024 at 9:20 am
Sarah DeMelo is reflecting on the moment she learned she was diagnosed with a rare form of cancer.
- mRNA vaccine tackles deadly brain cancer in human trialon May 6, 2024 at 6:45 am
Glioblastoma is one of the most deadly cancers, with few treatment options available. Now, a small human clinical trial has demonstrated an mRNA vaccine that quickly rallies the immune system to fight ...
- Prostate Cancer Newson May 2, 2024 at 5:00 pm
Promising New Options for Treating Aggressive Prostate Cancer Oct. 18, 2023 — Investigators have identified two promising new treatment options for men with recurrent prostate cancer -- both of ...
The Latest Google Headlines on:
TREATMENT OF AGGRESSIVE CANCER
[google_news title=”” keyword=”TREATMENT OF AGGRESSIVE CANCER” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]