Researchers discover unexpected role of an immune system receptor; blocking it halts human cancer cell growth and improves survival in animal models
For some cancers, initial treatment with chemotherapy brings positive, but only temporary, results: tumors shrink, but then rebound as the cancer becomes drug-resistant. This pattern of remission-resistance-relapse is particularly true for pancreatic cancer, an aggressive disease in which early success is often countered by eventual disease progression.
To wit: The one-year relative survival rate for pancreatic cancer is 20 percent, according to the American Cancer Society. The five-year rate is just 7 percent.
The reason: Current multidrug chemotherapy regimens targeting pancreatic cancer typically do not fully eradicate all cancer cells, leaving behind drug-resistant cells that harbor aberrant stem cell properties and can drive tumor regrowth and metastasis.
In a new paper publishing in the April 4, 2019 online issue of Cell, an international team of scientists led by researchers at University of California San Diego School of Medicine employed an array of next-generation sequencing and gene-editing tools, such as CRISPR, to map the molecular dependencies —and thus vulnerabilities — of pancreatic cancer stem cells.
Most notably, they found that a key hormone receptor called retinoic acid receptor-related orphan receptor gamma or ROR?, previously studied in inflammation and T-cell differentiation, was especially active during pancreatic cancer progression, and that blocking it markedly slowed patient derived tumor growth and improved survival in animal models.
“These studies revealed an unexpected role for immuno-regulatory genes in the maintenance of the most aggressive, drug-resistant cells in pancreatic cancer,” said senior study author Tannishtha Reya, PhD, UC San Diego professor in the departments of Pharmacology and Medicine. In particular, ROR? emerged as a key regulator. ROR? rose with cancer progression and its inhibition through genetic and pharmacological approaches resulted in a striking defect in pancreatic cancer growth.
“Our work shows that immune system signals are hijacked by pancreatic cancer, and suggests that therapies currently being tested for autoimmune indications should be considered for testing in pancreatic cancer,” said Reya.
Using genome scale approaches to map stem cell dependencies in pancreatic cancer “will be invaluable for understanding the basis of therapy resistance and recurrence and for discovering new vulnerabilities in pancreatic cancer,” said Reya. “Beyond providing new scientific insight, this work can help identify pathways for which clinical grade inhibitors may already exist and can thus be rapidly tested in pancreatic cancer.”
In particular, she said the discovery of ROR?‘s role in promoting tumor growth provides a new avenue for research and potential therapies. “One exciting aspect is the possibility that nuclear hormone receptors could represent therapeutic targets for pancreatic cancer. In fact, drugs targeting ROR? have already been developed by several pharmaceutical companies, and are in trials for autoimmune diseases. Our findings suggest that these agents could also be a valuable therapeutic strategy for pancreatic cancer.”
Learn more: Genome-Wide Analysis Reveals New Strategies to Target Pancreatic Cancer
The Latest on: Pancreatic cancer
[google_news title=”” keyword=”pancreatic cancer” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Pancreatic cancer
- 'Smart drugs' give new hope to some patients with advanced pancreatic canceron June 7, 2023 at 12:48 am
A promising new targeted cancer therapy will soon be available to certain patients with advanced pancreatic cancer—from the comfort of their home. The treatment will be available through a ...
- Walk held to raise awareness for pancreatic canceron June 6, 2023 at 7:22 am
For the people whose lives have forever been by pancreatic cancer, any amount of awareness and support is enough to give them hope to keep fighting.
- Experts hopeful about MRNA vaccine for pancreatic canceron June 4, 2023 at 10:52 am
Dr. Ali Khan joined 'Fox News Live' to discuss the potential treatment and why he is 'hopeful' on the clinical trial for cancer patients.
- Neoadjuvant Chemo Flops Versus Upfront Surgery for Resectable Pancreatic Canceron June 4, 2023 at 9:36 am
Neoadjuvant chemotherapy failed to match upfront surgery for survival in resectable pancreatic cancer, a small randomized trial showed. Unexpectedly, patients assigned to surgery first lived more than ...
- The race to cure pancreatic cancer: Polly’s Run returns for 14th yearon June 3, 2023 at 10:31 pm
That’s exactly what Polly’s sons have done in the 14 years since she lost her life to pancreatic cancer. Since 2009, the annual 5K held in her honor — on the anniversary of her passing — has raised ...
- What are the chances of a pancreatic cyst becoming cancerous? Find out what the experts sayon June 1, 2023 at 2:28 pm
Answered by Dr. Raghu BhokyaMBBS · 7 years of experience · IndiaMost of the pancreatic cyst are benign. Less then 20% pancreatic cyst becomes cancerous. Untreated benign cyst may progress to cancerous ...
- Pancreatic cancer microbiome discovery holds treatment hopeon May 30, 2023 at 9:00 am
NtRON Biotechnology has announced the identification of prophage and (non-) ORF-jamphage from the microbiome frequently observed in long-term pancreatic cancer survivors. The company said the ...
- Andy Rourke, The Smiths bassist, dies from pancreatic cancer: Signs and symptoms of the conditionon May 30, 2023 at 4:26 am
The Smiths bassist Andy Rourke has died aged 59 after battling pancreatic cancer," his former bandmate Johnny Marr has shared. "It is with deep sadness that that we announce the passing of Andy ...
- Revolutionizing Pancreatic Cancer Treatment With Personalized mRNA Vaccineson May 25, 2023 at 3:26 am
An NIH-funded team from Memorial Sloan Kettering Cancer Center has developed a personalized mRNA cancer vaccine for pancreatic ductal adenocarcinoma (PDAC), in collaboration with BioNTech. The ...
via Bing News