Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer.

Affiliations

1. Research Oncology, Genentech, Inc., 1 DNA Way, Mailstop 72, South San Francisco, CA 94080, USA.
Authors
Junttila TT¹
(1 author)

Breast Cancer Research and Treatment, 21 Aug 2010, 128(2):347-356
https://doi.org/10.1007/s10549-010-1090-x PMID: 20730488

Abstract

Trastuzumab (Herceptin(®)) is currently used as a treatment for patients whose breast tumors overexpress HER2/ErbB2. Trastuzumab-DM1 (T-DM1, trastuzumab emtansine) is designed to combine the clinical benefits of trastuzumab with a potent microtubule-disrupting drug, DM1 (a maytansine derivative). Currently T-DM1 is being tested in multiple clinical trials. The mechanisms of action for trastuzumab include inhibition of PI3K/AKT signaling pathway, inhibition of HER-2 shedding and Fcγ receptor mediated engagement of immune cells, which may result in antibody-dependent cellular cytotoxicity (ADCC). Here we report that T-DM1 retains the mechanisms of action of unconjugated trastuzumab and is active against lapatinib resistant cell lines and tumors.

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References

Articles referenced by this article (34)

Molecular portraits of human breast tumours.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D
Nature, (6797):747-752 2000
MED: 10963602
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL
Science, (4785):177-182 1987
MED: 3798106
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A
Science, (4905):707-712 1989
MED: 2470152
Humanization of an anti-p185HER2 antibody for human cancer therapy.
Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME, Shepard HM
Proc Natl Acad Sci U S A, (10):4285-4289 1992
MED: 1350088
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab.
Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ
Nature, (6924):756-760 2003
MED: 12610629
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD; Herceptin Adjuvant (HERA) Trial Study Team
N Engl J Med, (16):1659-1672 2005
MED: 16236737
Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, [...] Wolmark N
N Engl J Med, (16):1673-1684 2005
MED: 16236738
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L
N Engl J Med, (11):783-792 2001
MED: 11248153
Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.
Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkio S, Flander M, Helle L, Ingalsuo S, Johansson K, Jaaskelainen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators
N Engl J Med, (8):809-820 2006
MED: 16495393
Sliwkowski MX, Lofgren J, Lewis GD, Hotaling TE, Fendly BM, Fox JA (1999) Nonclinical studies addressing the mechanism of action of Herceptin® (Trastuzumab). Semin Oncol 26(Suppl 12):60–70

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This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.
Cai A, Chen Y, Wang LS, Cusick JK, Shi Y
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Review
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC

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Search life-sciences literature (45,094,167 articles, preprints and more)

Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer.

Affiliations

Abstract

Full text links

References

Molecular portraits of human breast tumours.

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.

Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.

Humanization of an anti-p185HER2 antibody for human cancer therapy.

Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab.

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.

Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.

Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.

Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.

Sliwkowski MX, Lofgren J, Lewis GD, Hotaling TE, Fendly BM, Fox JA (1999) Nonclinical studies addressing the mechanism of action of Herceptin® (Trastuzumab). Semin Oncol 26(Suppl 12):60–70

Citations & impact

Impact metrics

Citations of article over time

Alternative metrics

Article citations

Understanding the chemistry & pharmacology of antibody-drug conjugates in triple-negative breast cancer with special reference to exatecan derivatives.

Comparative Analysis and Future Prospects of Human Epidermal Growth Factor Receptor 2 (HER2) and Trophoblast Cell-Surface Antigen 2 (Trop-2) Targeted Antibody-Drug Conjugates in Breast Cancer Treatment.

Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance.

Identification of key genes and pathways involved in T-DM1-resistance in OE-19 esophageal cancer cells through bioinformatics analysis.

Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.

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Search life-sciences literature (45,094,167 articles, preprints and more)

Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer.

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Affiliations

Abstract

Full text links

References

Sliwkowski MX, Lofgren J, Lewis GD, Hotaling TE, Fendly BM, Fox JA (1999) Nonclinical studies addressing the mechanism of action of Herceptin® (Trastuzumab). Semin Oncol 26(Suppl 12):60–70

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