The Biology and Therapeutic Implications of Tumor Dormancy and Reactivation

Overview

Journal Front Oncol

Specialty Oncology

Date 2018 Apr 5

PMID 29616190

Citations 23

Authors

Amit S Yadav

Poonam R Pandey

Ramesh Butti

N N V Radharani

Shamayita Roy

Shaileshkumar R Bhalara

Mahadeo Gorain

Gopal C Kundu

Dhiraj Kumar

Affiliations

Soon will be listed here.

Abstract

Advancements in the early detection of cancer coupled with improved surgery, radiotherapy, and adjuvant therapy led to substantial increase in patient survival. Nevertheless, cancer metastasis is the leading cause of death in several cancer patients. The majority of these deaths are associated with metastatic relapse kinetics after a variable period of clinical remission. Most of the cancer recurrences are thought to be associated with the reactivation of dormant disseminated tumor cells (DTCs). In this review, we have summarized the cellular and molecular mechanisms related to DTCs and the role of microenvironmental niche. These mechanisms regulate the dormant state and help in the reactivation, which leads to metastatic outgrowth. Identification of novel therapeutic targets to eliminate these dormant tumor cells will be highly useful in controlling the metastatic relapse-related death with several cancers.

Citing Articles

Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence.

Tufail M, Jiang C, Li N Mil Med Res. 2025; 12(1):7.

PMID: 39934876 PMC: 11812268. DOI: 10.1186/s40779-025-00595-2.

Advancements in Circulating Tumor Cell Research: Bridging Biology and Clinical Applications.

Salu P, Reindl K Cancers (Basel). 2024; 16(6).

PMID: 38539545 PMC: 10969710. DOI: 10.3390/cancers16061213.

Outlook and opportunities for engineered environments of breast cancer dormancy.

Richbourg N, Irakoze N, Kim H, Peyton S Sci Adv. 2024; 10(10):eadl0165.

PMID: 38457510 PMC: 10923521. DOI: 10.1126/sciadv.adl0165.

An engineered niche delineates metastatic potential of breast cancer.

Orbach S, DeVaull C, Bealer E, Ross B, Jeruss J, Shea L Bioeng Transl Med. 2024; 9(1):e10606.

PMID: 38193115 PMC: 10771563. DOI: 10.1002/btm2.10606.

Muscle and Bone Defects in Metastatic Disease.

Pauk M, Saito H, Hesse E, Taipaleenmaki H Curr Osteoporos Rep. 2022; 20(5):273-289.

PMID: 35994202 PMC: 9522697. DOI: 10.1007/s11914-022-00741-y.

References

Gao D, Nolan D, Mellick A, Bambino K, McDonnell K, Mittal V . Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science. 2008; 319(5860):195-8. DOI: 10.1126/science.1150224. View

Malladi S, Macalinao D, Jin X, He L, Basnet H, Zou Y . Metastatic Latency and Immune Evasion through Autocrine Inhibition of WNT. Cell. 2016; 165(1):45-60. PMC: 4808520. DOI: 10.1016/j.cell.2016.02.025. View

Holmgren L, OReilly M, Folkman J . Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995; 1(2):149-53. DOI: 10.1038/nm0295-149. View

Patel P, Chen E . Cancer stem cells, tumor dormancy, and metastasis. Front Endocrinol (Lausanne). 2012; 3:125. PMC: 3478572. DOI: 10.3389/fendo.2012.00125. View

Giancotti F . Mechanisms governing metastatic dormancy and reactivation. Cell. 2013; 155(4):750-64. PMC: 4354734. DOI: 10.1016/j.cell.2013.10.029. View

Hickson J, Huo D, Vander Griend D, Lin A, Rinker-Schaeffer C, Yamada S . The p38 kinases MKK4 and MKK6 suppress metastatic colonization in human ovarian carcinoma. Cancer Res. 2006; 66(4):2264-70. DOI: 10.1158/0008-5472.CAN-05-3676. View

Gao H, Chakraborty G, Lee-Lim A, Mo Q, Decker M, Vonica A . The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell. 2012; 150(4):764-79. PMC: 3711709. DOI: 10.1016/j.cell.2012.06.035. View

Kobayashi A, Okuda H, Xing F, Pandey P, Watabe M, Hirota S . Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med. 2011; 208(13):2641-55. PMC: 3244043. DOI: 10.1084/jem.20110840. View

Aguirre-Ghiso J . Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer. 2007; 7(11):834-46. PMC: 2519109. DOI: 10.1038/nrc2256. View

10.

Ocana O, Corcoles R, Fabra A, Moreno-Bueno G, Acloque H, Vega S . Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell. 2012; 22(6):709-24. DOI: 10.1016/j.ccr.2012.10.012. View

11.

Sosa M, Avivar-Valderas A, Bragado P, Wen H, Aguirre-Ghiso J . ERK1/2 and p38α/β signaling in tumor cell quiescence: opportunities to control dormant residual disease. Clin Cancer Res. 2011; 17(18):5850-7. PMC: 3226348. DOI: 10.1158/1078-0432.CCR-10-2574. View

12.

Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert W, Goldbrunner R, Herms J . Real-time imaging reveals the single steps of brain metastasis formation. Nat Med. 2009; 16(1):116-22. DOI: 10.1038/nm.2072. View

13.

Kumar S, Sharma P, Kumar D, Chakraborty G, Gorain M, Kundu G . Functional characterization of stromal osteopontin in melanoma progression and metastasis. PLoS One. 2013; 8(7):e69116. PMC: 3720680. DOI: 10.1371/journal.pone.0069116. View

14.

Deng X, Ewton D, Friedman E . Mirk/Dyrk1B maintains the viability of quiescent pancreatic cancer cells by reducing levels of reactive oxygen species. Cancer Res. 2009; 69(8):3317-24. PMC: 2669831. DOI: 10.1158/0008-5472.CAN-08-2903. View

15.

Studebaker A, Storci G, Werbeck J, Sansone P, Sasser A, Tavolari S . Fibroblasts isolated from common sites of breast cancer metastasis enhance cancer cell growth rates and invasiveness in an interleukin-6-dependent manner. Cancer Res. 2008; 68(21):9087-95. DOI: 10.1158/0008-5472.CAN-08-0400. View

16.

Morrison S, Spradling A . Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 2008; 132(4):598-611. PMC: 4505728. DOI: 10.1016/j.cell.2008.01.038. View

17.

Gay L, Malanchi I . The sleeping ugly: Tumour microenvironment's act to make or break the spell of dormancy. Biochim Biophys Acta Rev Cancer. 2017; 1868(1):231-238. DOI: 10.1016/j.bbcan.2017.05.002. View

18.

Kelly T, Suva L, Huang Y, MacLeod V, Miao H, Walker R . Expression of heparanase by primary breast tumors promotes bone resorption in the absence of detectable bone metastases. Cancer Res. 2005; 65(13):5778-84. DOI: 10.1158/0008-5472.CAN-05-0749. View

19.

Kumar D, Gorain M, Kundu G, Kundu G . Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma. Mol Cancer. 2017; 16(1):7. PMC: 5282877. DOI: 10.1186/s12943-016-0578-3. View

20.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View