Rethinking the Metastatic Cascade As a Therapeutic Target

Overview

Journal Nat Rev Clin Oncol

Specialty Oncology

Date 2011 Apr 20

PMID 21502993

Citations 52

Authors

Lida A Mina

George W Sledge Jr

Affiliations

Soon will be listed here.

Abstract

Metastasis is the leading cause of cancer death. The metastatic cascade is a complex yet inefficient process that we have only begun to understand in recent years. Several of the early steps of this cascade are not readily targetable in the clinic. Past therapeutic developmental strategies have not distinguished between micrometastases and overt metastases. This lack of understanding is apparent in therapies that have been developed for patients with metastatic disease that are not efficacious in patients with micrometastatic disease; that is, in the adjuvant setting. Moreover, drugs that target distant metastases often do not work in the adjuvant setting. This Review will discuss our current understanding of the metastatic cascade as it relates to therapy, emerging therapeutic targets in the metastatic process, and how novel antimetastatic therapies might be developed for clinical use.

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References

Gumireddy K, Sun F, Klein-Szanto A, Gibbins J, Gimotty P, Saunders A . In vivo selection for metastasis promoting genes in the mouse. Proc Natl Acad Sci U S A. 2007; 104(16):6696-701. PMC: 1871848. DOI: 10.1073/pnas.0701145104. View

Bishop G, Hostager B . Molecular mechanisms of CD40 signaling. Arch Immunol Ther Exp (Warsz). 2001; 49(2):129-37. View

Naumov G, Townson J, MacDonald I, Wilson S, Bramwell V, Groom A . Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Res Treat. 2004; 82(3):199-206. DOI: 10.1023/B:BREA.0000004377.12288.3c. View

Kobayashi H, Saga T, Kawamoto S, Sato N, Hiraga A, Ishimori T . Dynamic micro-magnetic resonance imaging of liver micrometastasis in mice with a novel liver macromolecular magnetic resonance contrast agent DAB-Am64-(1B4M-Gd)(64). Cancer Res. 2001; 61(13):4966-70. View

Ellis L . Mechanisms of action of bevacizumab as a component of therapy for metastatic colorectal cancer. Semin Oncol. 2006; 33(5 Suppl 10):S1-7. DOI: 10.1053/j.seminoncol.2006.08.002. View

Coppin C, Porzsolt F, Awa A, Kumpf J, Coldman A, Wilt T . Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev. 2005; (1):CD001425. DOI: 10.1002/14651858.CD001425.pub2. View

Kerbel R . Tumor angiogenesis: past, present and the near future. Carcinogenesis. 2000; 21(3):505-15. DOI: 10.1093/carcin/21.3.505. View

Loges S, Mazzone M, Hohensinner P, Carmeliet P . Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell. 2009; 15(3):167-70. DOI: 10.1016/j.ccr.2009.02.007. View

Ma L, Teruya-Feldstein J, Weinberg R . Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007; 449(7163):682-8. DOI: 10.1038/nature06174. View

10.

Rosenberg S, Yang J, Topalian S, Schwartzentruber D, Weber J, Parkinson D . Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994; 271(12):907-13. View

11.

Conway E, Collen D, Carmeliet P . Molecular mechanisms of blood vessel growth. Cardiovasc Res. 2001; 49(3):507-21. DOI: 10.1016/s0008-6363(00)00281-9. View

12.

Patel S, Ndabahaliye A, Lim P, Milton R, Rameshwar P . Challenges in the development of future treatments for breast cancer stem cells. Breast Cancer (Dove Med Press). 2014; 2:1-11. PMC: 3004231. View

13.

Koebel C, Vermi W, Swann J, Zerafa N, Rodig S, Old L . Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007; 450(7171):903-7. DOI: 10.1038/nature06309. View

14.

Schneider B, Sledge Jr G . Anti-VEGF therapy as adjuvant therapy: clouds on the horizon?. Breast Cancer Res. 2009; 11(3):303. PMC: 2716490. DOI: 10.1186/bcr2250. View

15.

Marshall J, Lee J, Steeg P . Clinical-translational strategies for the elevation of Nm23-H1 metastasis suppressor gene expression. Mol Cell Biochem. 2009; 329(1-2):115-20. PMC: 3501675. DOI: 10.1007/s11010-009-0116-3. View

16.

Ebos J, Lee C, Cruz-Munoz W, Bjarnason G, Christensen J, Kerbel R . Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009; 15(3):232-9. PMC: 4540346. DOI: 10.1016/j.ccr.2009.01.021. View

17.

Rudin C, Hann C, Laterra J, Yauch R, Callahan C, Fu L . Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med. 2009; 361(12):1173-8. PMC: 5317279. DOI: 10.1056/NEJMoa0902903. View

18.

Miller K, Gradishar W, Schuchter L, Sparano J, Cobleigh M, Robert N . A randomized phase II pilot trial of adjuvant marimastat in patients with early-stage breast cancer. Ann Oncol. 2002; 13(8):1220-4. DOI: 10.1093/annonc/mdf199. View

19.

Guise T, Mohammad K, Clines G, Stebbins E, Wong D, Higgins L . Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clin Cancer Res. 2006; 12(20 Pt 2):6213s-6216s. DOI: 10.1158/1078-0432.CCR-06-1007. View

20.

Palmieri D, Lockman P, Thomas F, Hua E, Herring J, Hargrave E . Vorinostat inhibits brain metastatic colonization in a model of triple-negative breast cancer and induces DNA double-strand breaks. Clin Cancer Res. 2009; 15(19):6148-57. PMC: 7356672. DOI: 10.1158/1078-0432.CCR-09-1039. View