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Cancer-associated fibroblasts in breast cancer:Challenges and opportunities

Cancer Communications 2022年第5期42卷 401-434页

作者： Dengdi Hu Zhaoqing Li Bin zheng Xixi Lin Yuehong Pan Peirong Gong Wenying Zhuo Yujie Hu Cong Chen Lini Chen Jichun Zhou Linbo Wang Affiliated Cixi Hospital Wenzhou Medical UniversityNingboZhejiang 315300P.R.China Affiliated Sir Run Run Shaw Hospital Zhejiang University School of Medicine(Key Laboratory of Cancer Prevention and InterventionMinistry of Education)HangzhouZhejiang 310016P.R.China Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province HangzhouZhejiang 310016P.R.China

The tumor microenvironment is proposed to contribute substantially to the progression of cancers,including breast cancer.Cancer-associated fibroblasts(CAFs)are the most abundant components of the tumor microenvironment.Studies have revealed that CAFs in breast cancer originate from several types of cells and promote breast cancer malignancy by secreting factors,generating exosomes,releasing nutrients,reshaping the extracellular matrix,and suppressing the function of immune cells.CAFs are also becoming therapeutic targets for breast cancer due to their specific distribution in tumors and their unique biomarkers.Agents interrupting the effect of CAFs on surrounding cells have been developed and applied in clinical trials.Here,we reviewed studies examining the heterogeneity of CAFs in breast cancer and expression patterns of CAF markers in different subtypes of breast cancer.We hope that summarizing CAFrelated studies from a historical perspective will help to accelerate the development of CAF-targeted therapeutic strategies for breast cancer.

关键词： Cancer-associated fibroblasts breast cancer therapeutic target tumor microenvironment biomarker tumor heterogeneity

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The crosstalk between autophagy and ferroptosis:what can we learn to target drug resistance in cancer?

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Cancer Biology & Medicine 2019年第4期16卷 630-646页

作者： Yulu Zhou Yong Shen Cong Chen Xinbing Sui Jingjing Yang Linbo Wang Jichun Zhou Department of Surgical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Provinee Hangzhou 310016China Department of Breast Surgery First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006China Department of medical Oncology Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western MedicineThe Affiliated Hospital of Hangzhou Normal UniversityCollege of MedicineHangzhou Normal UniversityHangzhou 310012China Department of Cancer Pharmacology Holistic Integrative Pharmacy InstitutesCollege of MedicineHangzhou Normal UniversityHangzhou 310012China Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Provinee and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Provinee Hangzhou Normal UniversityHangzhou 310012China

Autophagy is a conserved intracellular degradation system that plays a dual role in cell death;thus,therapies targeting autophagy in cancer are somewhat controversial.Ferroptosis is a new form of regulated cell death featured with the iron-dependent accumulation of lethal lipid ROS.This pathway is morphologically,biochemically and genetically distinct from other forms of cell death.Accumulating studies have revealed crosstalk between autophagy and ferroptosis at the molecular level.In this review,we summarize the mechanisms of ferroptosis and autophagy,and more importantly,their roles in the drug resistance of cancer.Numerous connections between ferroptosis and autophagy have been revealed,and a strong causal relationship exists wherein one process controls the other and can be utilized as potential therapeutic targets for cancer.The elucidation of when and how to modulate their crosstalk using therapeutic strategies depends on an understanding of the fine-tuned switch between ferroptosis and autophagy,and approaches designed to manipulate the intensity of autophagy might be the key.

关键词： Autophagy ferroptosis crosstalk cancer drug resistance

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