Preclinical Study Reveals Why Chemotherapy May Be Compromised in Patients With Pancreatic Cancer

Preclinical Study Reveals Why Chemotherapy May Be Compromised in Patients With Pancreatic  The ASCO Post 

OK , put on your thinking caps. It is actually well explained here but you have to go step by step> Also a key takeaway is the funding came from the State of Texas- well Hot  damn Y’all- how cool is that, Dr. Ryan

Alright- we are talking abut laboratory research. We are talking about one of the most resistant if not most resistant non rare and almost always lethal cancer Pancreatic cancer, We are looking at the one drug most commonly used because even without killing any of the cancer it was approved because it definitely could make patients feel better. The drug works by killing cells that are dividing – cancer cells typically do so more than normal cells. Ok stay with me , cancer cells can go through a transition from epithelial or lining cells to an different kind of more primitive cells called mesenchymal cells. When they do  it leads to cancer cells no longer having babies- more new cancer cells – so a drug like gemcitabine would understandably not work well in a tumor if that tumor’s cells commonly make that transition in type  AND  it is hard to target therapy to a non dividing cells , you need very cancer type cell specific targets that are tolerable. Make sense so far? Good So, to be sneaky, if we could inhibit this transition of cancer cells in pancreatic cancer cells which love to do this, gemcitabine and other drugs like it might work So now you can read this sentence and get it- remember cancer cells will act as immature as they have to get away with being cancer cells and spreading – remember that. “Epithelial-to-mesenchymal transition is an embryonic cellular plasticity program that is hijacked by cancer cells and is thought to help cancer cells migrate to other organs. When cancer cells adopt an epithelial-to-mesenchymal transition program to promote their migration, they generally stop dividing”. So  of course the research findings indicated that epithelial-to-mesenchymal transition leads to arrest of cancer cell proliferation, causing impaired sensitivity to chemotherapy, impacting the body’s ability to effectively respond to such treatment. Voilas!  How is that for some elegant brilliant lab research Dr Ryan

This elegance is why this lab bench research is published in the most prestigious  NATURE journal Dr Ryan

Key Points:
  • Preclinical research indicated that epithelial-to-mesenchymal transition leads to arrest of cancer cell proliferation, causing impaired sensitivity to chemotherapy, impacting the body’s ability to effectively respond to such treatment, and potentially leading to poor outcomes.
  • Inhibiting epithelial-to-mesenchymal transition program led to enhanced response of tumors to gemcitabine.

A study at The University of Texas MD Anderson Cancer Center may explain why chemotherapy drugs such as gemcitabine are not effective for many patients with pancreatic cancer and perhaps point to new approaches to treatment, including enhancing gemcitabine’s ability to stop tumor growth.

The MD Anderson study in mice suggested that suppressing a cellular plasticity process known as epithelial-to-mesenchymal transition, in combination with gemcitabine, may boost the drug’s effectiveness. These study findings were published by Zheng et al in Nature.

It gets better, they found , of course cling-ons. NE’ER-DO-WELLs, other bad guys who loved the epithelial to mesenchymal transition in the cancer cells are helping it out.“We found that EMT program suppressed drug transporter and concentrative proteins, which inadvertently protected these cancer cells from antiproliferative drugs such as gemcitabine,” You are now all PhD’s who figure this out , in this case with a state grant and one day this will probably contribute to a cure of one of the most  gruesome of all solid tumor and you heard the SCIENCE here This is why you need to buy the book

“Diagnosis of pancreatic cancer is associated with poor prognosis despite the availability of current therapies,” said Raghu Kalluri, MD, PhD, Professor and Chair of Cancer Biology at MD Anderson. “Therefore, new treatment strategies are urgently needed.”

Study Details

Dr. Kalluri’s team looked at epithelial-to-mesenchymal transition, an embryonic cellular plasticity program that is hijacked by cancer cells and is thought to help cancer cells migrate to other organs. When cancer cells adopt an epithelial-to-mesenchymal transition program to promote their migration, they generally stop dividing. The research findings indicate that epithelial-to-mesenchymal transition leads to arrest of cancer cell proliferation, causing impaired sensitivity to chemotherapy, impacting the body’s ability to effectively respond to such treatment.

“Gemcitabine works primarily on cancer cells that are dividing or proliferating,” said Dr. Kalluri. “When cancer cells suspend their proliferation—such as when they launch an epithelial-to-mesenchymal transition program—then antiproliferation drugs like gemcitabine do not target them well.”

“We found that EMT program suppressed drug transporter and concentrative proteins, which inadvertently protected these cancer cells from antiproliferative drugs such as gemcitabine,” added Dr. Kalluri. “The correlation of decreased survival of pancreatic cancer patients with an increased EMT program is likely due to their impaired capacity to respond to chemotherapy, leading to overall poor prognosis and higher incidence of metastasis.”

Inhibiting the epithelial-to-mesenchymal transition program led to an enhanced response of tumors to gemcitabine.  But of course

“Collectively, our study offers the opportunity to evaluate the potential of targeting EMT program to enhance efficacy of chemotherapy and likely targeted therapies,” said Dr. Kalluri.

The study was funded by the Cancer Prevention and Research Institute of Texas.

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