餓死腫瘤，養活細胞：癌症如何抵抗藥物 Starve a tumor, feed a cell: How cancers can resist drugs

News Release 3-Mar-2020

UCI biologists discover new approach for overcoming drug resistance

University of California – Irvine

Irvine, Calif., March 3, 2020 — With drug resistance a major challenge in the fight against cancer, a discovery by University of California, Irvine biologists could offer new approaches to overcoming the obstacle. Their research reveals that a mechanism enabling the diseased cells to scavenge dead cell debris for nourishment holds a pivotal role. The study by Aimee Edinger, associate professor of developmental & cell biology, and researcher Vaishali Jayashankar appears in Nature Communications.

(Link to open access study: https://www.nature.com/articles/s41467-020-14928-3)

“Cancer cells require a tremendous amount of nutrients,” Edinger said. “Chemotherapy and other treatments that damage DNA force tumor cells to rev up their metabolism to make the repairs necessary to survive and grow. Targeting DNA metabolism in this way often works for a while, but in virtually all patients, tumor cells become resistant and the treatment becomes ineffective.”

In probing the problem, the two scientists examined a process called macropinocytosis. It enables a cancer cell desperate for nourishment to scoop up dead cell material within a tumor and feed on it.

“Tumors contain a lot of dead cells because the blood supply is abnormal, causing many cancer cells to starve to death,” Edinger said. “Using this method of scavenging, cancer cells can obtain the amino acids, sugars, fatty acids and nucleotides they require to keep growing.”

This new research revealed that macropinocytosis makes a previously unappreciated contribution to breast cancer drug-resistance. Edinger and Jayashankar also demonstrated that the same process could thwart treatments for pancreas and prostate cancer.

“What we see is that blocking macropinocytosis can help us to treat many different cancers more effectively,” Edinger said. “This knowledge could enable better biomarker selection in clinical drug trials currently underway, leading to improved response to pharmaceutical combinations. It also provides a strong rationale for developing drugs that target and block macropinocytosis.”

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Support for the research was provided by Congressionally Directed Medical Research Programs (CDMRP), the University of California Cancer Research Coordinating Committee, the Chao Family Comprehensive Cancer Center Anti-Cancer Challenge, and UCI Applied Innovation.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 222 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

餓死腫瘤，養活細胞：癌症如何抵抗藥物

加利福尼亞州爾灣市，2020年3月3日-加利福尼亞大學歐文分校的生物學家為發現抗藥性是對抗癌症的主要挑戰，生物學家的一項發現可以為克服這一障礙提供新的方法。他們的研究表明，使患病細胞清除死細胞碎片以進行營養的機制具有舉足輕重的作用。發育與細胞生物學副教授艾米·愛丁格（Aimee Edinger）和研究員Vaishali Jayashankar的研究出現在《自然通訊》上。

（鏈接到開放獲取研究：https://www.nature.com/articles/s41467-020-14928-3）

“癌細胞需要大量的營養，”愛丁格說。化學療法和其他破壞DNA的療法迫使腫瘤細胞加快新陳代謝，從而為生存和生長進行必要的修復。以這種方式靶向DNA代謝通常會持續一段時間，但實際上在所有患者中，腫瘤細胞都具有耐藥性，治療效果不佳。”

在探討這個問題時，兩位科學家檢查了一個稱為巨胞飲的過程。它使渴望營養的癌細胞能夠吸收腫瘤中的死細胞物質並以此為食。

愛丁格說：“由於血液供應異常，腫瘤含有大量死細胞，導致許多癌細胞餓死。” “使用這種清除方法，癌細胞可以獲得保持生長所需的氨基酸，糖，脂肪酸和核苷酸。”

這項新的研究表明，巨胞飲對乳腺癌的耐藥性做出了前所未有的貢獻。 Edinger和Jayashankar還證明了相同的過程可能會阻礙胰腺和前列腺癌的治療。

“我們發現阻斷巨噬細胞增多可以幫助我們更有效地治療許多不同的癌症，”愛丁格說。 “這項知識可以使目前正在進行的臨床藥物試驗中更好地選擇生物標誌物，從而改善對藥物組合的反應。它還為開發靶向和阻斷巨胞飲的藥物提供了有力的依據。”

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