Autotaxin (ATX) as a Marker for Breast Cancer

NCT ID: NCT04328194

Last Updated: 2020-03-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-01

Study Completion Date

2022-11-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Breast cancer is the leading cause of cancer death in women worldwide. According to the GLOBOCAN 2018 worldwide estimates of cancer incidence and mortality, in 2018, about 2,088,849 new cases were diagnosed and approximately 626,679 women were predicted to die from the disease . It is the leading cause of cancer related mortality, representing15% of deaths per year worldwide .

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Breast cancer is the most common malignancy in females in Egypt. It accounts for 32 % of cancer in women . Breast cancer in Egypt carries an unfavorable prognosis with 29% mortality and 3.7:1 incidence to mortality ratio .

Despite the rising incidence of breast cancer, the survival rates have improved in recent years due to the deep research in biological behavior of breast cancer . Although the current 5-year survival for primary breast cancer is relatively high (ranging from 80% to 92% in different populations) survival rates decrease to less than 25% when the disease becomes metastatic .These data support the need to develop more efficient strategies for preventive, intervention, evaluation of therapy, and prediction of prognosis .

Autotaxin (ATX) is a glycoprotein encoded by the ENPP2 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 2) gene located on chromosome 8. Identical to lysophospholipase D, ATX plays a role in the synthesis of the bioactive lipid mediator lysophosphatidate (LPA) from lysophosphatidylcholine (LPC) .

LPA acts through specific G protein-coupled receptors (GPCRs) to promote cellular proliferation, migration, and survival . ATX expression was also reported higher in poorly differentiated tumors and, in independent studies, is correlated with invasiveness of cancer cells suggesting a higher metastatic potential of ATX-expressing tumors . ATX is generated from platelets, endothelial cells, fibroblasts, and adipocytes and specifically, ATX from adipocytes has an impact on plasma LPA level . Thus, adipocytes could be an important origin of ATX in tumors. Breast cancer is a human cancer that has adipocyte-rich stroma. Adipose tissue comprises 56% of non-lactating breast tissue, and 35% of lactating breast tissue . ATX-LPA signaling has been reported to be involved in angiogenesis, tumor cell invasion, and migration in breast cancer .

Increased ATX expression has also been reported in various forms of cancer, such as glioblastoma, hepatocellular and thyroid carcinomas, pancreatic and hematological cancers. A large number of evidence indicate that ATX-LPA is associated with chemotherapy resistance of cancer, and in breast cancer, ATX can reverse cell apoptosis.

In a mouse model, α-bromomethylene phosphonate LPA (BrP-LPA), a dual ATX and pan-LPAR( Lysophosphatidic acid receptor ) inhibitor, inhibited migration and invasion of breast cancer cell lines and suppressed primary tumor and angiogenesis in a mouse xenograft study . Since tumor and stromal cells in breast cancer express ATX-LPA signaling-related proteins, inhibition of the ATX-LPA axis could be of therapeutic importance .Therefore, further study ATX as a tumor marker in breast cancer is required.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Breast Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Study Group

80 patients with breast cancer

Group Type EXPERIMENTAL

Serum Autotaxin

Intervention Type DIAGNOSTIC_TEST

Marker

chest x-ray

Intervention Type RADIATION

chest x- ray will be done for the study group

Breast ultrasound or mammography

Intervention Type DIAGNOSTIC_TEST

Breast ultrasound or mammography will be done for the study group to diagnosis of breast cancer

Histopathological examination of breast mass specimens

Intervention Type DIAGNOSTIC_TEST

by True cut or fine needle aspiration cytology

Magnetic Resonance Imaging ( MRI) and Bone scan

Intervention Type RADIATION

will be done for the study group

Peripheral haemogram

Intervention Type DIAGNOSTIC_TEST

blood sample will be taken from the patients

Renal and liver functions

Intervention Type DIAGNOSTIC_TEST

to exclude any other morbidity

Prothrombin time and concentration

Intervention Type DIAGNOSTIC_TEST

blood sample will be taken from the patients

Cancer Antigen 15-3 (CA15-3).

Intervention Type DIAGNOSTIC_TEST

will be done for the 2 groups

Full medical history

Intervention Type OTHER

full medical history will be taken from all patients

Full clinical examination

Intervention Type OTHER

full clinical examination will be done for the patients

Control Group

20 healthy controls aged ( 19 to 69 years ) from healthy volunteers after informed consent.

Group Type PLACEBO_COMPARATOR

Serum Autotaxin

Intervention Type DIAGNOSTIC_TEST

Marker

Cancer Antigen 15-3 (CA15-3).

Intervention Type DIAGNOSTIC_TEST

will be done for the 2 groups

Full medical history

Intervention Type OTHER

full medical history will be taken from all patients

Full clinical examination

Intervention Type OTHER

full clinical examination will be done for the patients

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Serum Autotaxin

Marker

Intervention Type DIAGNOSTIC_TEST

chest x-ray

chest x- ray will be done for the study group

Intervention Type RADIATION

Breast ultrasound or mammography

Breast ultrasound or mammography will be done for the study group to diagnosis of breast cancer

Intervention Type DIAGNOSTIC_TEST

Histopathological examination of breast mass specimens

by True cut or fine needle aspiration cytology

Intervention Type DIAGNOSTIC_TEST

Magnetic Resonance Imaging ( MRI) and Bone scan

will be done for the study group

Intervention Type RADIATION

Peripheral haemogram

blood sample will be taken from the patients

Intervention Type DIAGNOSTIC_TEST

Renal and liver functions

to exclude any other morbidity

Intervention Type DIAGNOSTIC_TEST

Prothrombin time and concentration

blood sample will be taken from the patients

Intervention Type DIAGNOSTIC_TEST

Cancer Antigen 15-3 (CA15-3).

will be done for the 2 groups

Intervention Type DIAGNOSTIC_TEST

Full medical history

full medical history will be taken from all patients

Intervention Type OTHER

Full clinical examination

full clinical examination will be done for the patients

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* The study will be conducted on one hundred female individuals; 80 newly diagnosed breast cancer patients before any treatment or surgical intervention and 20 apparently normal female individuals.

Exclusion Criteria

* Patients with any other type of malignant or benign tumors, renal failure, cardiovascular diseases and liver cirrhosis were excluded from our study.
* Past history of chemotherapy or surgical treatment of any malignancy.
* Inflammatory diseases (e.g.bronchitis) or autoimmune diseases (e.g.rheumatoid arthritis).
Minimum Eligible Age

19 Years

Maximum Eligible Age

69 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Assiut University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Mary Gamal Sudky

principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Hanan Hareth, MD

Role: CONTACT

Phone: 01002954322

Email: [email protected]

Tahra Sherif

Role: CONTACT

Phone: 01227446166

Email: [email protected]

References

Explore related publications, articles, or registry entries linked to this study.

Boucharaba A, Serre CM, Gres S, Saulnier-Blache JS, Bordet JC, Guglielmi J, Clezardin P, Peyruchaud O. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest. 2004 Dec;114(12):1714-25. doi: 10.1172/JCI22123.

Reference Type RESULT
PMID: 15599396 (View on PubMed)

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

Reference Type RESULT
PMID: 30207593 (View on PubMed)

Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J. LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol. 2010;50:157-86. doi: 10.1146/annurev.pharmtox.010909.105753.

Reference Type RESULT
PMID: 20055701 (View on PubMed)

Dusaulcy R, Rancoule C, Gres S, Wanecq E, Colom A, Guigne C, van Meeteren LA, Moolenaar WH, Valet P, Saulnier-Blache JS. Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid. J Lipid Res. 2011 Jun;52(6):1247-1255. doi: 10.1194/jlr.M014985. Epub 2011 Mar 18.

Reference Type RESULT
PMID: 21421848 (View on PubMed)

Ferry G, Tellier E, Try A, Gres S, Naime I, Simon MF, Rodriguez M, Boucher J, Tack I, Gesta S, Chomarat P, Dieu M, Raes M, Galizzi JP, Valet P, Boutin JA, Saulnier-Blache JS. Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity. J Biol Chem. 2003 May 16;278(20):18162-9. doi: 10.1074/jbc.M301158200. Epub 2003 Mar 17.

Reference Type RESULT
PMID: 12642576 (View on PubMed)

Hinestrosa MC, Dickersin K, Klein P, Mayer M, Noss K, Slamon D, Sledge G, Visco FM. Shaping the future of biomarker research in breast cancer to ensure clinical relevance. Nat Rev Cancer. 2007 Apr;7(4):309-15. doi: 10.1038/nrc2113.

Reference Type RESULT
PMID: 17384585 (View on PubMed)

Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H. Cancer incidence in egypt: results of the national population-based cancer registry program. J Cancer Epidemiol. 2014;2014:437971. doi: 10.1155/2014/437971. Epub 2014 Sep 21.

Reference Type RESULT
PMID: 25328522 (View on PubMed)

Jansen S, Stefan C, Creemers JW, Waelkens E, Van Eynde A, Stalmans W, Bollen M. Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D. J Cell Sci. 2005 Jul 15;118(Pt 14):3081-9. doi: 10.1242/jcs.02438. Epub 2005 Jun 28.

Reference Type RESULT
PMID: 15985467 (View on PubMed)

Kazama S, Kitayama J, Aoki J, Mori K, Nagawa H. Immunohistochemical detection of autotaxin (ATX)/lysophospholipase D (lysoPLD) in submucosal invasive colorectal cancer. J Gastrointest Cancer. 2011 Dec;42(4):204-11. doi: 10.1007/s12029-010-9186-4.

Reference Type RESULT
PMID: 20623382 (View on PubMed)

Leblanc R, Peyruchaud O. New insights into the autotaxin/LPA axis in cancer development and metastasis. Exp Cell Res. 2015 May 1;333(2):183-189. doi: 10.1016/j.yexcr.2014.11.010. Epub 2014 Nov 25.

Reference Type RESULT
PMID: 25460336 (View on PubMed)

Lonning PE. Breast cancer prognostication and prediction: are we making progress? Ann Oncol. 2007 Sep;18 Suppl 8:viii3-7. doi: 10.1093/annonc/mdm260.

Reference Type RESULT
PMID: 17890212 (View on PubMed)

Mao Y, Keller ET, Garfield DH, Shen K, Wang J. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 2013 Jun;32(1-2):303-15. doi: 10.1007/s10555-012-9415-3.

Reference Type RESULT
PMID: 23114846 (View on PubMed)

Nikitopoulou I, Oikonomou N, Karouzakis E, Sevastou I, Nikolaidou-Katsaridou N, Zhao Z, Mersinias V, Armaka M, Xu Y, Masu M, Mills GB, Gay S, Kollias G, Aidinis V. Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis. J Exp Med. 2012 May 7;209(5):925-33. doi: 10.1084/jem.20112012. Epub 2012 Apr 9.

Reference Type RESULT
PMID: 22493518 (View on PubMed)

Ramsay DT, Kent JC, Hartmann RA, Hartmann PE. Anatomy of the lactating human breast redefined with ultrasound imaging. J Anat. 2005 Jun;206(6):525-34. doi: 10.1111/j.1469-7580.2005.00417.x.

Reference Type RESULT
PMID: 15960763 (View on PubMed)

Reis-Filho JS, Pusztai L. Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 2011 Nov 19;378(9805):1812-23. doi: 10.1016/S0140-6736(11)61539-0.

Reference Type RESULT
PMID: 22098854 (View on PubMed)

Samadi N, Gaetano C, Goping IS, Brindley DN. Autotaxin protects MCF-7 breast cancer and MDA-MB-435 melanoma cells against Taxol-induced apoptosis. Oncogene. 2009 Feb 19;28(7):1028-39. doi: 10.1038/onc.2008.442. Epub 2008 Dec 15.

Reference Type RESULT
PMID: 19079345 (View on PubMed)

Teo K, Brunton VG. The role and therapeutic potential of the autotaxin-lysophosphatidate signalling axis in breast cancer. Biochem J. 2014 Oct 1;463(1):157-65. doi: 10.1042/BJ20140680.

Reference Type RESULT
PMID: 25195735 (View on PubMed)

van Meeteren LA, Moolenaar WH. Regulation and biological activities of the autotaxin-LPA axis. Prog Lipid Res. 2007 Mar;46(2):145-60. doi: 10.1016/j.plipres.2007.02.001. Epub 2007 Mar 16.

Reference Type RESULT
PMID: 17459484 (View on PubMed)

Vandeweyer E, Hertens D. Quantification of glands and fat in breast tissue: an experimental determination. Ann Anat. 2002 Mar;184(2):181-4. doi: 10.1016/S0940-9602(02)80016-4.

Reference Type RESULT
PMID: 11936199 (View on PubMed)

Windrichova J, Fuchsova R, Kucera R, Topolcan O, Fiala O, Finek J, Slipkova D, Karlikova M, Svobodova J. Testing of a Novel Cancer Metastatic Multiplex Panel for the Detection of Bone-metastatic Disease - a Pilot Study. Anticancer Res. 2016 Apr;36(4):1973-8.

Reference Type RESULT
PMID: 27069189 (View on PubMed)

Xia Q, Deng AM, Wu SS, Zheng M. Cholera toxin inhibits human hepatocarcinoma cell proliferation in vitro via suppressing ATX/LPA axis. Acta Pharmacol Sin. 2011 Aug;32(8):1055-62. doi: 10.1038/aps.2011.31. Epub 2011 Jul 18.

Reference Type RESULT
PMID: 21765444 (View on PubMed)

Shao Y, Yu Y, He Y, Chen Q, Liu H. Serum ATX as a novel biomarker for breast cancer. Medicine (Baltimore). 2019 Mar;98(13):e14973. doi: 10.1097/MD.0000000000014973.

Reference Type RESULT
PMID: 30921203 (View on PubMed)

Zhang S, Li L, Wang T, Bian L, Hu H, Xu C, Liu B, Liu Y, Cristofanilli M, Jiang Z. Real-time HER2 status detected on circulating tumor cells predicts different outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer patients. BMC Cancer. 2016 Jul 25;16:526. doi: 10.1186/s12885-016-2578-5.

Reference Type RESULT
PMID: 27456503 (View on PubMed)

Zhang H, Xu X, Gajewiak J, Tsukahara R, Fujiwara Y, Liu J, Fells JI, Perygin D, Parrill AL, Tigyi G, Prestwich GD. Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. Cancer Res. 2009 Jul 1;69(13):5441-9. doi: 10.1158/0008-5472.CAN-09-0302. Epub 2009 Jun 9.

Reference Type RESULT
PMID: 19509223 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

medicin

Identifier Type: -

Identifier Source: org_study_id