Attacking Breast Cancer at the Preinvasion Stage by Targeting Autophagy

Overview

Journal Womens Health (Lond)

Specialty Gynecology & Obstetrics

Date 2013 Mar 13

PMID 23477322

Citations 6

Authors

Virginia Espina

John Wysolmerski

Kirsten Edmiston

Lance A Liotta

Affiliations

Soon will be listed here.

Abstract

Preinvasive breast carcinoma cells that proliferate and accumulate within the nonvascular, closed intraductal niche are under severe hypoxic and metabolic stress. Understanding the survival mechanisms used by these cells has revealed therapeutic strategies for killing preinvasive neoplasms. We have found that autophagy ('self-eating') is a major survival strategy used by preinvasive carcinoma and breast cancer stem-like cells. Based on this finding, we have opened a clinical trial that is exploring neoadjuvant oral chloroquine antiautophagy therapy for ductal carcinoma in situ. We envision that antiautophagy therapy can be administered in combination with other treatments such as those that elevate intracellular calcium, to create a state of intolerable stress for preinvasive neoplastic cells, and thereby stop breast cancer before it starts.

Citing Articles

The Function of Autophagy in the Initiation, and Development of Breast Cancer.

Beilankouhi E, Valilo M, Dastmalchi N, Teimourian S, Safaralizadeh R Curr Med Chem. 2023; 31(20):2974-2990.

PMID: 37138421 DOI: 10.2174/0929867330666230503145319.

Chloroquine sensitizes MDA-MB-231 cells to osimertinib through autophagy-apoptosis crosstalk pathway.

Fleisher B, Mody H, Werkman C, Ait-Oudhia S Breast Cancer (Dove Med Press). 2019; 11:231-241.

PMID: 31839713 PMC: 6664863. DOI: 10.2147/BCTT.S211030.

Organotypic microfluidic breast cancer model reveals starvation-induced spatial-temporal metabolic adaptations.

Ayuso J, Gillette A, Lugo-Cintron K, Acevedo-Acevedo S, Gomez I, Morgan M EBioMedicine. 2018; 37:144-157.

PMID: 30482722 PMC: 6284542. DOI: 10.1016/j.ebiom.2018.10.046.

Hypoxia activates cadherin-22 synthesis via eIF4E2 to drive cancer cell migration, invasion and adhesion.

Kelly N, Varga J, Specker E, Romeo C, Coomber B, Uniacke J Oncogene. 2017; 37(5):651-662.

PMID: 28991229 PMC: 5770212. DOI: 10.1038/onc.2017.372.

Non-enzymatic, serum-free tissue culture of pre-invasive breast lesions for spontaneous generation of mammospheres.

Espina V, Edmiston K, Liotta L J Vis Exp. 2014; (93):e51926.

PMID: 25406584 PMC: 4353433. DOI: 10.3791/51926.

References

Dickson R, Johnson M, Maemura M, Low J . Anti-invasion drugs. Breast Cancer Res Treat. 1996; 38(1):121-32. DOI: 10.1007/BF01803790. View

Tannock I, Kopelyan I . Influence of glucose concentration on growth and formation of necrosis in spheroids derived from a human bladder cancer cell line. Cancer Res. 1986; 46(6):3105-10. View

Monteith G, McAndrew D, Faddy H, Roberts-Thomson S . Calcium and cancer: targeting Ca2+ transport. Nat Rev Cancer. 2007; 7(7):519-30. DOI: 10.1038/nrc2171. View

Pinder S . Ductal carcinoma in situ (DCIS): pathological features, differential diagnosis, prognostic factors and specimen evaluation. Mod Pathol. 2010; 23 Suppl 2:S8-13. DOI: 10.1038/modpathol.2010.40. View

Feig S, Saitas V, FINKEL G, Schwartz G . Stability of malignant breast microcalcifications. Radiology. 1994; 192(1):153-6. DOI: 10.1148/radiology.192.1.8208928. View

Augustijns P, Geusens P, Verbeke N . Chloroquine levels in blood during chronic treatment of patients with rheumatoid arthritis. Eur J Clin Pharmacol. 1992; 42(4):429-33. DOI: 10.1007/BF00280130. View

Maclean K, Dorsey F, Cleveland J, Kastan M . Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. J Clin Invest. 2007; 118(1):79-88. PMC: 2148253. DOI: 10.1172/JCI33700. View

Kelloff G, Sigman C . Assessing intraepithelial neoplasia and drug safety in cancer-preventive drug development. Nat Rev Cancer. 2007; 7(7):508-18. DOI: 10.1038/nrc2154. View

Vaupel P, Kallinowski F, Okunieff P . Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989; 49(23):6449-65. View

10.

Rabinowitz J, White E . Autophagy and metabolism. Science. 2010; 330(6009):1344-8. PMC: 3010857. DOI: 10.1126/science.1193497. View

11.

Brini M, Carafoli E . Calcium pumps in health and disease. Physiol Rev. 2009; 89(4):1341-78. DOI: 10.1152/physrev.00032.2008. View

12.

OShaughnessy J, Kelloff G, Gordon G, Dannenberg A, Hong W, Fabian C . Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin Cancer Res. 2002; 8(2):314-46. View

13.

Lyng H, Sundfor K, Trope C, Rofstad E . Oxygen tension and vascular density in human cervix carcinoma. Br J Cancer. 1996; 74(10):1559-63. PMC: 2074838. DOI: 10.1038/bjc.1996.589. View

14.

Bikle D . Vitamin D metabolism and function in the skin. Mol Cell Endocrinol. 2011; 347(1-2):80-9. PMC: 3188673. DOI: 10.1016/j.mce.2011.05.017. View

15.

Espina V, Mariani B, Gallagher R, Tran K, Banks S, Wiedemann J . Malignant precursor cells pre-exist in human breast DCIS and require autophagy for survival. PLoS One. 2010; 5(4):e10240. PMC: 2857649. DOI: 10.1371/journal.pone.0010240. View

16.

VanHouten J, Sullivan C, Bazinet C, Ryoo T, Camp R, Rimm D . PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer. Proc Natl Acad Sci U S A. 2010; 107(25):11405-10. PMC: 2895115. DOI: 10.1073/pnas.0911186107. View

17.

Ducharme J, Farinotti R . Clinical pharmacokinetics and metabolism of chloroquine. Focus on recent advancements. Clin Pharmacokinet. 1996; 31(4):257-74. DOI: 10.2165/00003088-199631040-00003. View

18.

Savarino A, Lucia M, Giordano F, Cauda R . Risks and benefits of chloroquine use in anticancer strategies. Lancet Oncol. 2006; 7(10):792-3. DOI: 10.1016/S1470-2045(06)70875-0. View

19.

McPhee C, Logan M, Freeman M, Baehrecke E . Activation of autophagy during cell death requires the engulfment receptor Draper. Nature. 2010; 465(7301):1093-6. PMC: 2892814. DOI: 10.1038/nature09127. View

20.

Liotta L, Tryggvason K, Garbisa S, Hart I, FOLTZ C, Shafie S . Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 1980; 284(5751):67-8. DOI: 10.1038/284067a0. View