Retinoids Induced Cancer Stem Cell Differentiation and Apoptosis for Cancer Therapies

  • Xin Cao Project Leader of Targeted Drug Design and Validation, Zhongshan Hospital Institute of Clinical Science, Fudan University Shanghai Medical College, Shanghai, 200032, China
Keywords: Retinoids, cancer stem cell, differentiation, apoptosis


Retinoids show great potential in various kinds of cancer chemotherapy due to its ability to induce signals for cell differentiation or death, as well as inhibit cancer stem cell proliferation. This paper summarized the recent progress of retinoids induced cancer stem cell differentiation and apoptosis in cancer therapy field, with the highlighted novel retinoid named WYC-209 in our lab, which could inhibit the tumor stem cell and malignant melanoma tumors with high efficacy and little toxicity.


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DeLuca LM. Retinoids and their receptors in differentiation, embryogenesis

and neoplasia. FASEB J. 5, 2924–33 (1991).

Hansen LA, Sigman CC, Andreola F, Ross SA, Kelloff GJ, De Luca LM.

Retinoids in chemoprevention and differentiation therapy. Carcinogenesis

, 1271–9 (2000).

Hanahan D, Weinberg, RA. Hallmarks of cancer: the next generation.

Cell 144, 646–674 (2011).

Visvader JE, Lindeman, GJ. Cancer stem cells: current status and

evolving complexities. Cell Stem Cell 10, 717–728 (2012).

Dean M, Fojo T, Bates S. Tumor stem cells and drug resistance. Nat. Rev.

Cancer 5, 275–284 (2005).

Liu, J. TanY, Zhang H, ZhangY, Xu P, Chen J, Poh YC, Tang K,Wang N,

Huang B. Soft fibrin gels promote selection and growth of tumorigenic

cells. Nat. Mater. 11, 734–741 (2012).

Tan Y, Tajik A, Chen J, Jia Q, Chowdhury F, Wang L, Chen J, Zhang S,

HongY,Yi H,Wu DC, ZhangY,Wei F, PohYC, Seong J, Singh R, Lin LJ,

Doˇganay S, LiY, Jia H, Ha T,WangY, Huang B,Wang N. Matrix softness

regulates plasticity of tumour-repopulating cells via H3K9 demethylation

and Sox2 expression. Nat. Commun. 5, 4619 (2014).

Chen J, Zhou W, Jia Q, Chen J, Zhang S, Yao W, Wei F, Zhang Y,

Yang F, HuangW, ZhangY, Zhang H, ZhangY, Huang B, Zhang Z, Jia H,

Wang N. Efficient extravasation of tumor-repopulating cells depends on

cell deformability. Sci. Rep. 6, 19304 (2016).

Bonnet D, Dick JE. Human acute myeloid leukemia is organized as

a hierarchy that originates from a primitive hematopoietic cell. Nat.

Med. 3, 730–7.

Ignatova TN, Kukekov VG, Laywell ED, Suslov ON, Vrionis FD,

Steindler DA. Human cortical glial tumors contain neural stem-like cells

expressing astroglial and neuronal markers in vitro. Glia. 39, 193–206


Sundar SJ, Hsieh JK, Manjila S, Lathia JD, Sloan A. The role of cancer

stem cells in glioblastoma. Neurosurgical Focus. 37, E6 (2014).

Retinoids Induced Cancer Stem Cell Differentiation 7

de Thé, H. Differentiation therapy revisited. Nat. Rev. Cancer 18,

–127 (2018).

Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH,

Ogden A, Shepherd L, Willman C, Bloomfield CD, Wiernik PH. Alltrans-

retinoic acid in acute promyelocytic leukemia. New Engl. J. Med.

, 1021–1028 (1997).

Wei S, Kozono S, Kats L, Nechama M, Li W, Guarnerio J, Luo

M, You MH, Yao Y, Kondo A, Hu H, Bozkurt G, Moerke NJ, Cao

S, Reschke M, Chen CH, Rego EM, Lo-Coco F, Cantley LC, Lee TH,Wu

H, Zhang Y, Pandolfi PP, Zhou XZ, Lu KP. Active Pin1 is a key target of

all-trans retinoic acid in acute promyelocytic leukemia and breast cancer.

Nat. Med. 21, 457–466 (2015).

Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating

evidence and unresolved questions. Nat. Rev. Cancer 8, 755–768


Chen JW, Cao X,An QL, ZhangY, Li K,YaoWT, Shi FC, Pan YF, Jia Q,

Zhou WW, Yang F, Wei FX, Wang N, Yu B. Inhibition of cancer stem

cell like cells by a synthetic retinoid. Nat. Commun. 11, 1406 (2018).

Lehmann-Che J, Bally C, de Thé H. Therapy resistance in APL. N. Engl.

J. Med. 371, 1171–1172 (2014).

Holohan C,Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug

resistance: an evolving paradigm. Nat. Rev. Cancer 13, 714–726 (2013).

Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and

evolving paradigms. Cell 147, 275–292 (2011).

Guenounou S, Delabesse E, Récher C. Sorafenib plus all-trans retinoic

acid for AML patients with FLT3-ITD and NPM1mutations. Eur J

Haematol. 93, 533–536 (2014).

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