Receptor Tyrosine Kinases: Characterisation, Mechanism of Action and Therapeutic Interests for Bone Cancers

Overview

Journal J Bone Oncol

Publisher Elsevier

Date 2015 Nov 19

PMID 26579483

Citations 56

Authors

Aude I Segaliny

Marta Tellez-Gabriel

Marie-Francoise Heymann

Dominique Heymann

Affiliations

Soon will be listed here.

Abstract

Bone cancers are characterised by the development of tumour cells in bone sites, associated with a dysregulation of their environment. In the last two decades, numerous therapeutic strategies have been developed to target the cancer cells or tumour niche. As the crosstalk between these two entities is tightly controlled by the release of polypeptide mediators activating signalling pathways through several receptor tyrosine kinases (RTKs), RTK inhibitors have been designed. These inhibitors have shown exciting clinical impacts, such as imatinib mesylate, which has become a reference treatment for chronic myeloid leukaemia and gastrointestinal tumours. The present review gives an overview of the main molecular and functional characteristics of RTKs, and focuses on the clinical applications that are envisaged and already assessed for the treatment of bone sarcomas and bone metastases.

Citing Articles

New Compounds with Enhanced Biological Activity Through the Strategic Introduction of Silylated Groups into Hydroxystearic Acids.

Zalambani C, Anconelli L, Calonghi N, Telese D, Micheletti G, Boga C Molecules. 2025; 30(3).

PMID: 39942547 PMC: 11820896. DOI: 10.3390/molecules30030440.

Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma.

Han Z, Yan Z, Ma Z, Wang Y, Beus M, Lu J Leukemia. 2025; 39(3):720-733.

PMID: 39885295 DOI: 10.1038/s41375-025-02522-9.

Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.

Zhang X, Jin T, Wang H, Han S, Liang Y Front Pharmacol. 2024; 15:1499799.

PMID: 39669194 PMC: 11635611. DOI: 10.3389/fphar.2024.1499799.

Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials.

Mehta K, Hegde M, Girisa S, Vishwa R, AlQahtani M, Abbas M Mil Med Res. 2024; 11(1):76.

PMID: 39668367 PMC: 11636053. DOI: 10.1186/s40779-024-00582-z.

Recent Applications of In Silico Approaches for Studying Receptor Mutations Associated with Human Pathologies.

Pappalardo M, Sipala F, Nicolosi M, Guccione S, Ronsisvalle S Molecules. 2024; 29(22).

PMID: 39598735 PMC: 11596970. DOI: 10.3390/molecules29225349.

References

Grignani G, Palmerini E, Dileo P, Asaftei S, DAmbrosio L, Pignochino Y . A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. Ann Oncol. 2011; 23(2):508-16. DOI: 10.1093/annonc/mdr151. View

Sonpavde G, Periman P, Bernold D, Weckstein D, Fleming M, Galsky M . Sunitinib malate for metastatic castration-resistant prostate cancer following docetaxel-based chemotherapy. Ann Oncol. 2009; 21(2):319-324. DOI: 10.1093/annonc/mdp323. View

Dikic I, Giordano S . Negative receptor signalling. Curr Opin Cell Biol. 2003; 15(2):128-35. DOI: 10.1016/s0955-0674(03)00004-8. View

Aragon-Ching J, Jain L, Gulley J, Arlen P, Wright J, Steinberg S . Final analysis of a phase II trial using sorafenib for metastatic castration-resistant prostate cancer. BJU Int. 2009; 103(12):1636-40. PMC: 2818665. DOI: 10.1111/j.1464-410X.2008.08327.x. View

Lemmon M, Schlessinger J . Cell signaling by receptor tyrosine kinases. Cell. 2010; 141(7):1117-34. PMC: 2914105. DOI: 10.1016/j.cell.2010.06.011. View

Mathew P, Thall P, Jones D, Perez C, Bucana C, Troncoso P . Platelet-derived growth factor receptor inhibitor imatinib mesylate and docetaxel: a modular phase I trial in androgen-independent prostate cancer. J Clin Oncol. 2004; 22(16):3323-9. DOI: 10.1200/JCO.2004.10.116. View

Dahut W, Scripture C, Posadas E, Jain L, Gulley J, Arlen P . A phase II clinical trial of sorafenib in androgen-independent prostate cancer. Clin Cancer Res. 2008; 14(1):209-14. DOI: 10.1158/1078-0432.CCR-07-1355. View

Bradshaw R, Chalkley R, Biarc J, Burlingame A . Receptor tyrosine kinase signaling mechanisms: Devolving TrkA responses with phosphoproteomics. Adv Biol Regul. 2012; 53(1):87-96. PMC: 3577974. DOI: 10.1016/j.jbior.2012.10.006. View

Han J, Tian R, Yong B, Luo C, Tan P, Shen J . Gas6/Axl mediates tumor cell apoptosis, migration and invasion and predicts the clinical outcome of osteosarcoma patients. Biochem Biophys Res Commun. 2013; 435(3):493-500. DOI: 10.1016/j.bbrc.2013.05.019. View

10.

Pignochino Y, Grignani G, Cavalloni G, Motta M, Tapparo M, Bruno S . Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways. Mol Cancer. 2009; 8:118. PMC: 2804605. DOI: 10.1186/1476-4598-8-118. View

11.

Pircher M, Mlineritsch B, Fridrik M, Dittrich C, Lang A, Petru E . Lapatinib-plus-pegylated liposomal doxorubicin in advanced HER2-positive breast cancer following trastuzumab: a phase II trial. Anticancer Res. 2015; 35(1):517-21. View

12.

Furugaki K, Moriya Y, Iwai T, Yorozu K, Yanagisawa M, Kondoh K . Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292. Clin Exp Metastasis. 2011; 28(7):649-59. PMC: 3198194. DOI: 10.1007/s10585-011-9398-4. View

13.

Maris J, Courtright J, Houghton P, Morton C, Kolb E, Lock R . Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008; 51(1):42-8. DOI: 10.1002/pbc.21535. View

14.

Rettew A, Getty P, Greenfield E . Receptor tyrosine kinases in osteosarcoma: not just the usual suspects. Adv Exp Med Biol. 2014; 804:47-66. DOI: 10.1007/978-3-319-04843-7_3. View

15.

Cristofanilli M, Valero V, Mangalik A, Royce M, Rabinowitz I, Arena F . Phase II, randomized trial to compare anastrozole combined with gefitinib or placebo in postmenopausal women with hormone receptor-positive metastatic breast cancer. Clin Cancer Res. 2010; 16(6):1904-14. DOI: 10.1158/1078-0432.CCR-09-2282. View

16.

Fu M, Zhang W, Shan L, Song J, Shang D, Ying J . Mutation status of somatic EGFR and KRAS genes in Chinese patients with prostate cancer (PCa). Virchows Arch. 2014; 464(5):575-81. DOI: 10.1007/s00428-014-1566-x. View

17.

Timeus F, Crescenzio N, Fandi A, Doria A, Foglia L, Cordero di Montezemolo L . In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines. Oncol Rep. 2008; 19(2):353-9. View

18.

Chugh R, Wathen J, Maki R, Benjamin R, Patel S, Meyers P . Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a bayesian hierarchical statistical model. J Clin Oncol. 2009; 27(19):3148-53. DOI: 10.1200/JCO.2008.20.5054. View

19.

Bond M, Bernstein M, Pappo A, Schultz K, Krailo M, Blaney S . A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a Children's Oncology Group study. Pediatr Blood Cancer. 2007; 50(2):254-8. DOI: 10.1002/pbc.21132. View

20.

Keizman D, Ish-Shalom M, Pili R, Hammers H, Eisenberger M, Sinibaldi V . Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma. Eur J Cancer. 2012; 48(7):1031-7. DOI: 10.1016/j.ejca.2012.02.050. View