Harnessing the synergistic potential of NK1R antagonists and selective COX-2 inhibitors for simultaneous targeting of TNBC cells and cancer stem cells
Triple-negative breast cancer (TNBC) lacks the expression of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), rendering it unresponsive to endocrine therapy and HER2 targeted treatments. Though certain chemotherapeutics targeting the cell cycle have shown efficacy to a certain extent, the presence of chemotherapy-resistant cancer stem cells (CSCs) presents a significant challenge in tackling TNBC. Multiple lines of evidence suggest the upregulation of neuropeptide Substance P (SP), its NK-1 receptor (NK1R) and the Cyclooxygenase-2 (COX-2) enzyme in TNBC patients. Upregulation of the SP/NK1R system and COX-2 influences major signalling pathways involved in cell proliferation, growth, survival, angiogenesis, inflammation, metastasis and stem cell activity. The simultaneous activation and crosstalk between the pathways activated by SP/NK1R and COX-2 consequently increase the levels of key regulators of self-renewal pathways in CSCs, promoting stemness. The combination therapy with NK1R antagonists and COX-2 inhibitors can simultaneously target TNBC cells and CSCs, thereby enhancing treatment efficacy and reducing the risk of recurrence and relapse. This review discusses the rationale for combining NK1R antagonists and COX-2 inhibitors for the better management of TNBC and a novel strategy to deliver drug cargo precisely to the tumour site to address the challenges associated with off-target binding.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
|---|---|
| Enthalten in: |
Journal of drug targeting - 32(2024), 3 vom: 13. Feb., Seite 258-269 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Singh, Madhu Tanya [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 16.02.2024 Date Revised 16.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/1061186X.2024.2309568 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367430185 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367430185 | ||
| 003 | DE-627 | ||
| 005 | 20240216232741.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240123s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/1061186X.2024.2309568 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1295.xml |
| 035 | |a (DE-627)NLM367430185 | ||
| 035 | |a (NLM)38252517 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Singh, Madhu Tanya |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Harnessing the synergistic potential of NK1R antagonists and selective COX-2 inhibitors for simultaneous targeting of TNBC cells and cancer stem cells |
| 264 | 1 | |c 2024 | |
| 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 16.02.2024 | ||
| 500 | |a Date Revised 16.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Triple-negative breast cancer (TNBC) lacks the expression of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), rendering it unresponsive to endocrine therapy and HER2 targeted treatments. Though certain chemotherapeutics targeting the cell cycle have shown efficacy to a certain extent, the presence of chemotherapy-resistant cancer stem cells (CSCs) presents a significant challenge in tackling TNBC. Multiple lines of evidence suggest the upregulation of neuropeptide Substance P (SP), its NK-1 receptor (NK1R) and the Cyclooxygenase-2 (COX-2) enzyme in TNBC patients. Upregulation of the SP/NK1R system and COX-2 influences major signalling pathways involved in cell proliferation, growth, survival, angiogenesis, inflammation, metastasis and stem cell activity. The simultaneous activation and crosstalk between the pathways activated by SP/NK1R and COX-2 consequently increase the levels of key regulators of self-renewal pathways in CSCs, promoting stemness. The combination therapy with NK1R antagonists and COX-2 inhibitors can simultaneously target TNBC cells and CSCs, thereby enhancing treatment efficacy and reducing the risk of recurrence and relapse. This review discusses the rationale for combining NK1R antagonists and COX-2 inhibitors for the better management of TNBC and a novel strategy to deliver drug cargo precisely to the tumour site to address the challenges associated with off-target binding | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a COX-2 enzyme | |
| 650 | 4 | |a Cancer stem cells | |
| 650 | 4 | |a neurokinin-1 receptor | |
| 650 | 4 | |a triple-negative breast cancer | |
| 650 | 4 | |a triple-negative breast cancer cells | |
| 650 | 7 | |a Cyclooxygenase 2 Inhibitors |2 NLM | |
| 650 | 7 | |a Cyclooxygenase 2 |2 NLM | |
| 650 | 7 | |a EC 1.14.99.1 |2 NLM | |
| 650 | 7 | |a Receptors, Estrogen |2 NLM | |
| 700 | 1 | |a Thaggikuppe Krishnamurthy, Praveen |e verfasserin |4 aut | |
| 700 | 1 | |a Magham, Sai Varshini |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of drug targeting |d 1996 |g 32(2024), 3 vom: 13. Feb., Seite 258-269 |w (DE-627)NLM074733958 |x 1029-2330 |7 nnns |
| 773 | 1 | 8 | |g volume:32 |g year:2024 |g number:3 |g day:13 |g month:02 |g pages:258-269 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/1061186X.2024.2309568 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 32 |j 2024 |e 3 |b 13 |c 02 |h 258-269 | ||