研究發現由輻射引起的炎症可導致三陰性乳腺癌 Study finds inflammation caused by radiation can drive triple-negative breast cancer

News Release 24-Feb-2020

ChristianaCare’s Cawley Center for Translational Cancer Research

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Wilmington, DE, February 24, 2020 — While radiation is successfully used to treat breast cancer by killing cancer cells, inflammation caused as a side-effect of radiation can have a contrary effect by promoting the survival of triple-negative breast cancer cells, according to research published online in the International Journal of Radiation Biology by Jennifer Sims-Mourtada, Ph.D., director of Translational Breast Cancer Research at ChristianaCare’s Helen F. Graham Cancer Center & Research Institute.

Accounting for 15-20% of all breast cancers, triple-negative breast cancer is faster growing than other types of breast cancers.

Dr. Sims-Mourtada’s latest study, “Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells,” brings scientists closer to understanding the mechanisms behind this aggressive and hard-to-treat cancer. It shows that inflammation caused by radiation can trigger stem-cell-like characteristics in non-stem breast cancer cells.

“This is the good and the bad of radiation,” Dr. Sims-Mourtada said. “We know radiation induced inflammation can help the immune system to kill tumor cells — that’s good — but also it can protect cancer stem cells in some cases, and that’s bad.”

She added, “What’s exciting about these findings is we’re learning more and more that the environment the tumor is in – its microenvironment – is very important. Historically, research has focused on the genetic defects in the tumor cells. We’re now also looking at the larger microenvironment and its contribution to cancer.”

The term triple-negative breast cancer refers to the fact that the cancer cells don’t have estrogen or progesterone receptors and also don’t make too much of the protein called HER2. The cells test “negative” on all 3 tests. These cancers tend to be more common in women under age 40, who are African-American, Latina or who have a BRCA1 mutation.

“My work focuses on cancer stem cells and their origination,” Dr. Sims-Mourtada said. “They exist in many cancers, but they’re particularly elusive in triple-negative breast cancer. Their abnormal growth capacity and survival mechanisms make them resistant to radiation and chemotherapy and help drive tumor growth.”

She and her team applied radiation to triple-negative breast cancer stem cells and to non-stem cells. In both cases, they found radiation induced an inflammatory response that activated the Il-6/Stat3 pathway, which plays a significant role in the growth and survival of cancer stem cells in triple-negative breast cancers. They also found that inhibiting STAT3 blocks the creation of cancer stem cells. Still unclear is the role IL-6/STAT3 plays in transforming a non-stem cell to a stem-cell.

For women living in Delaware, Dr. Sims-Mourtada’s research is especially urgent: The rates of triple-negative breast cancer in the state are the highest nationwide.

“At ChristianaCare, we are advancing cancer research to help people in our community today, while we also advance the fight against cancer nationwide,” said Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute. “Dr. Sims-Mourtada’s research is a dramatic step toward better treatments for triple-negative breast cancer.”

To advance her research on inflammation, last year Dr. Sims-Mourtada received a $659,538 grant from the Lisa Dean Moseley Foundation. The three-year grant will enable her and her team at the Cawley Center for Translational Cancer Research to continue investigating the role of cells immediately around a tumor in spurring the growth of triple-negative breast cancer and a possible therapy for this particularly difficult cancer.

“Our next step is to understand the inflammatory response and how we might inhibit it to keep new cancer stem cells from developing,” Dr. Sims-Mourtada said.

Dr. Sims-Mourtada’s research team previously identified an anti-inflammatory drug, currently used to treat rheumatoid arthritis, that has the potential to target and inhibit the growth of cancer stem cells and triple-negative breast cancer tumors. That research could set the stage for clinical investigation of the drug, alone or in combination with chemotherapy, to improve outcomes for patients with triple-negative breast cancer.

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Download images of Dr. Sims-Mourtada in the lab and of triple negative breast cancer cells.

About the Helen F. Graham Cancer Center & Research Institute

The Helen F. Graham Cancer Center & Research Institute, a National Cancer Institute Community Oncology Research Program, is part of ChristianaCare, one of the country’s most dynamic health systems, centered on improving health outcomes, making high-quality care more accessible and lowering health care costs. With more than 232,000 patient visits last year, the Graham Cancer Center is recognized as a national model for multidisciplinary cancer care and a top enroller in U.S. clinical research trials. In conjunction with its Gene Editing Institute, the Cawley Center for Translational Cancer Research, the Tissue Procurement Center, statewide High-Risk Family Cancer Registry and collaborations with world-renowned scientists at facilities such as The Wistar Institute in Philadelphia scientists are opening new avenues to more quickly translate cancer science into cancer medicine. For more information, visit christianacare.org/cancer.

研究發現由輻射引起的炎症可導致三陰性乳腺癌

特拉華州威爾明頓市,2020年2月24日—儘管輻射通過殺死癌細胞成功用於治療乳腺癌,但作為輻射副作用引起的炎症可能會通過促進三陰性乳腺癌細胞的存活而產生相反的影響。克里斯蒂安娜·卡雷(ChristianaCare)的海倫·格雷厄姆(Helen F. Graham)癌症中心和研究所的轉化性乳腺癌研究主任詹妮弗·西姆斯·穆塔達(Jennifer Sims-Mourtada)博士在線發表在《國際放射生物學雜誌》上的研究。

三陰性乳腺癌佔所有乳腺癌的15-20%,其增長速度快於其他類型的乳腺癌。

Sims-Mourtada博士的最新研究表明:“輻射誘導炎症反應,導致STAT3依賴性乳腺癌幹細胞樣細胞的細胞可塑性和放射抵抗力發生變化。”使科學家們更加了解這種激進且難於治療的機制。治療癌症。它表明由輻射引起的炎症可以觸發非干乳腺癌細胞中的干細胞樣特徵。

Sims-Mourtada博士說:“這是輻射的好與壞。” “我們知道輻射誘發的炎症可以幫助免疫系統殺死腫瘤細胞-很好-但在某些情況下還可以保護癌幹細胞,這很糟糕。”

她補充說:“這些發現令人興奮的是,我們越來越了解到腫瘤所處的環境-其微環境-非常重要。歷史上,研究集中在腫瘤細胞的遺傳缺陷上。我們現在也正在研究更大的微環境及其對癌症的貢獻。”

術語三陰性乳腺癌是指癌細胞沒有雌激素或孕激素受體,並且也沒有太多的稱為HER2的蛋白質。單元格在所有3個測試中測試為“陰性”。這些癌症在40歲以下的女性中更為常見,這些女性是非裔美國人,拉丁裔或具有BRCA1突變的女性。

Sims-Mourtada博士說:“我的工作集中在癌症幹細胞及其起源上。” “它們存在於許多癌症中,但在三陰性乳腺癌中尤其難以捉摸。它們的異常生長能力和生存機制使其對放射線和化學療法具有抵抗力,並有助於推動腫瘤的生長。”

她和她的團隊將放射線應用於三陰性乳腺癌幹細胞和非干細胞。在這兩種情況下,他們都發現輻射誘導了激活Il-6 / Stat3途徑的炎症反應,這在三陰性乳腺癌的癌症幹細胞的生長和存活中起著重要作用。他們還發現抑制STAT3可以阻止癌症幹細胞的產生。 IL-6 / STAT3在將非干細胞轉化為乾細胞中所起的作用仍不清楚。

對於居住在特拉華州的女性,Sims-Mourtada博士的研究尤為緊迫:該州三陰性乳腺癌的發病率是全國最高的。

“在ChristianaCare,我們正在推進癌症研究,以幫助當今社區的人們,同時我們也在全國范圍內推進與癌症的鬥爭,”美國銀行授予海倫·格雷厄姆·格雷厄姆癌症中心醫學總監Nicholas J. Petrelli博士說。 & 研究機構。 “博士Sims-Mourtada的研究是朝著更好地治療三陰性乳腺癌的重要一步。”

為了推動她對炎症的研究,去年,西姆斯·穆爾塔達(Sims-Mourtada)博士從麗莎·迪恩·莫斯利基金會(Lisa Dean Moseley Foundation)獲得了659,538美元的贈款。這項為期三年的贈款將使她和她在Cawley轉化癌症研究中心的研究小組能夠繼續研究腫瘤周圍的細胞在促進三陰性乳腺癌的生長中的作用,並為這種特別困難的癌症提供可能的治療方法。

Sims-Mourtada博士說:“我們的下一步是了解炎症反應以及如何抑制炎症反應,以阻止新的癌症幹細胞發育。”

Sims-Mourtada博士的研究小組先前確定了一種抗炎藥,目前用於治療類風濕關節炎,它具有靶向和抑制癌症幹細胞和三陰性乳腺癌腫瘤生長的潛力。這項研究可以為藥物單獨或與化學療法聯用的臨床研究奠定基礎,以改善三陰性乳腺癌患者的預後。

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