Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Stromal cells within the tumor microenvironment play a supportive role in tumor growth, progression, and treatment resistance; therefore, these nonmalignant cells are potential therapeutic targets. In this issue of the JCI, Szot et al. devised a strategy to exploit the cell-surface marker
TEM8
(also known as ANTXR1), which is expressed by cancer-associated stromal cells, as a zip code to deliver an antibody-drug conjugate (ADC) linked to the potent cancer-killing drug monomethyl auristatin E (MMAE). In preclinical tumor and experimental metastasis models of multiple cancer types,
TEM8
-ADC targeted
TEM8
-expressing cancer-associated stromal cells, which processed and liberated membrane-permeable MMAE and released this drug via the
P-glycoprotein
(
P-gp
) drug transporter. Released MMAE killed cancer cells through a bystander mechanism that did minimal damage to the stromal cells themselves.
P-gp
-expressing tumor cells displayed MMAE resistance, suggesting that
P-gp
expression status may identify patients who might benefit the most from
TEM8
-ADC. This strategy, termed DAaRTS (drug activation and release through stroma), represents an elegant example of how selective expression of a cell-surface molecule on cancer-associated stroma can be exploited to facilitate drug delivery and shrink solid tumors.
...
PMID:Deadly DAaRTS destroy cancer cells via a tumor microenvironment-mediated trigger. 2986
