HER2 Tyrosine Kinase Inhibitors in the Sensitization to Cancers Resistant to HER2 Antibodies
Human epidermal growth factor receptor (HER2) is a well-established histopathological marker. It is aberrantly expressed in various cancers, predominantly in breast cancer. HER2 protein overexpression and/or HER2 gene amplification induces HER2 dimerization, tyrosine kinase (TK) phosphorylation, activation of different signaling pathways including the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, and hence, carcinogenesis. HER2 antibodies like trastuzumab and pertuzumab act on the extracellular domain (ECD) of the HER2 receptor. These were developed to treat HER2-overexpressing or amplified cancers. These effectively inhibit HER2 dimerization and, hence, further signaling. However, antibody resistance and, thereby, disease relapse have emerged as serious concerns. HER2 splicing, cross-signaling, and intracellular alterations are the most common factors causing HER2-antibody resistance. To overcome the therapeutic resistance associated with trastuzumab, TK inhibitors (TKIs) were developed. These bind to the intracellular TK domain and inhibit TK phosphorylation and, therefore, signaling. Though less selective, TKIs have been reported to show activity against HER2 spliced variants and inhibit breast cancers resistant to HER2 antibodies. However, these have not really been established as monotherapeutic agents and have remained as alternative therapeutics only on the account of resistance, toxicity, and poor pharmacokinetic profile. These issues can be resolved by employing combination treatment regimens including HER2-antibody and HER2 TKI. The HER2 TKI in conjunction with HER2 antibody sensitize the refractory HER2-positive cancers towards HER2-anti-body therapy. In addition, these act synergistically with the HER2-antibody resulting in an additive clinical response in patients. This chapter will explore various HER2 TKIs- lapatinib, neratinib, afatinib, sapitinib, CP-724,714, dacomitinib, tucatinib, pyrotinib, and poziotinib as promising clinical tools in sensitizing resistant cancers to HER2 antibodies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
|---|---|
| Enthalten in: |
Critical reviews in oncogenesis - 25(2020), 3 vom: 19., Seite 241-250 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Singla, Heena [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 30.11.2021 Date Revised 30.11.2021 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1615/CritRevOncog.2020037108 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM320264262 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM320264262 | ||
| 003 | DE-627 | ||
| 005 | 20231225173214.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1615/CritRevOncog.2020037108 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1067.xml |
| 035 | |a (DE-627)NLM320264262 | ||
| 035 | |a (NLM)33463944 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Singla, Heena |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HER2 Tyrosine Kinase Inhibitors in the Sensitization to Cancers Resistant to HER2 Antibodies |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 30.11.2021 | ||
| 500 | |a Date Revised 30.11.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Human epidermal growth factor receptor (HER2) is a well-established histopathological marker. It is aberrantly expressed in various cancers, predominantly in breast cancer. HER2 protein overexpression and/or HER2 gene amplification induces HER2 dimerization, tyrosine kinase (TK) phosphorylation, activation of different signaling pathways including the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, and hence, carcinogenesis. HER2 antibodies like trastuzumab and pertuzumab act on the extracellular domain (ECD) of the HER2 receptor. These were developed to treat HER2-overexpressing or amplified cancers. These effectively inhibit HER2 dimerization and, hence, further signaling. However, antibody resistance and, thereby, disease relapse have emerged as serious concerns. HER2 splicing, cross-signaling, and intracellular alterations are the most common factors causing HER2-antibody resistance. To overcome the therapeutic resistance associated with trastuzumab, TK inhibitors (TKIs) were developed. These bind to the intracellular TK domain and inhibit TK phosphorylation and, therefore, signaling. Though less selective, TKIs have been reported to show activity against HER2 spliced variants and inhibit breast cancers resistant to HER2 antibodies. However, these have not really been established as monotherapeutic agents and have remained as alternative therapeutics only on the account of resistance, toxicity, and poor pharmacokinetic profile. These issues can be resolved by employing combination treatment regimens including HER2-antibody and HER2 TKI. The HER2 TKI in conjunction with HER2 antibody sensitize the refractory HER2-positive cancers towards HER2-anti-body therapy. In addition, these act synergistically with the HER2-antibody resulting in an additive clinical response in patients. This chapter will explore various HER2 TKIs- lapatinib, neratinib, afatinib, sapitinib, CP-724,714, dacomitinib, tucatinib, pyrotinib, and poziotinib as promising clinical tools in sensitizing resistant cancers to HER2 antibodies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents, Immunological |2 NLM | |
| 650 | 7 | |a Oxazoles |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 650 | 7 | |a Quinazolines |2 NLM | |
| 650 | 7 | |a tucatinib |2 NLM | |
| 650 | 7 | |a 234248D0HH |2 NLM | |
| 650 | 7 | |a Receptor, ErbB-2 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Trastuzumab |2 NLM | |
| 650 | 7 | |a P188ANX8CK |2 NLM | |
| 700 | 1 | |a Munshi, Anjana |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Critical reviews in oncogenesis |d 1995 |g 25(2020), 3 vom: 19., Seite 241-250 |w (DE-627)NLM012938904 |x 0893-9675 |7 nnns |
| 773 | 1 | 8 | |g volume:25 |g year:2020 |g number:3 |g day:19 |g pages:241-250 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1615/CritRevOncog.2020037108 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 25 |j 2020 |e 3 |b 19 |h 241-250 | ||