Utility of serum protein-bound neutral hexoses and L-fucose for estimation of malignant tumor extension and evaluation of efficacy of therapy.
Summary The method used permits correction for the influence of the neutral hexoses, galactose and mannose, on the apparent concentration of protein-bound l-fucose, as estimated by the… Expand
A Transient Pseudosenescent Secretome Promotes Tumor Growth after Antiangiogenic Therapy Withdrawal.
It is shown that stopping VEGFR TKI treatment after resistance can lead to rebound tumor growth that is driven by cellular changes resembling senescence-associated secretory phenotypes (SASPs) known to promote cancer progression, which may account for the highly diverse and reversible cytokine changes observed in VEGF inhibitor-treated patients. Expand Enhanced efficacy of sitravatinib in metastatic models of antiangiogenic therapy resistance
Results suggest that the diverse and often inconsistent compensatory signaling mechanisms found to contribute to TKI resistance may paradoxically improve the tumor-inhibiting effects of broad-spectrum TKIs such as sitravatinib that are able to block multiple signaling pathways. Expand Tumor-Independent Host Secretomes Induced By Angiogenesis and Immune-Checkpoint Inhibitors
These are the first studies to assess and compare “off-target” host secretory effects of VEGF and PD-1 pathway inhibition that occur independent of tumor stage or tumor response to therapy, and show that host TIS signatures differ between drug target, drug class, and dose. Expand Abstract 326: Enhanced efficacy of Sitravatinib (MGCD516) in metastatic models of antiangiogenic therapy resistance
These studies suggest that broad-spectrum RTKI inhibitors such as sitravatinib that target multiple metastasis-promoting mechanisms improve efficacy after antiangiogenic treatment failure and improve outcomes in a second-line setting. Expand Abstract 4099: Intrinsic Tumor Cell Consequences of Acquired Resistance to PD-L1 Blockade
The in vivo derivation of cells from orthotopically implanted mouse mammary EMT-6 primary tumors in mice that were initially responsive to PD-L1 inhibition but eventually developed resistance are described to reveal that acquired resistance to PD -L1 blockade can result in PD- L1-regulated intrinsic tumor cell changes involving secretory proteins and controlled, at least in part, by IFN signaling. Expand Acquired resistance to PD-L1 inhibition is associated with an enhanced type I IFN-stimulated secretory program in tumor cells
It is shown that prolonged PD-L1 inhibition can ‘rewire’ existing intracellular IFN:PD-L 1 signaling crosstalk to drive secretory programs that help protect tumors from immune cell attack and represent a targetable vulnerability to overcome acquired resistance in patients. Expand Abstract 326: Enhanced efficacy of Sitravatinib (MGCD516) in metastatic models of antiangiogenic therapy resistance
These studies suggest that broad-spectrum RTKI inhibitors such as sitravatinib that target multiple metastasis-promoting mechanisms improve efficacy after antiangiogenic treatment failure and improve outcomes in a second-line setting. Expand 249 Targeting IFNβ-regulated secretory profiles to overcome acquired anti-PD-L1 resistance
A secretory profile associated with acquired resistance to PD-L1 blockade that may be modulated, at least in part, by IFNβ is identified and selective targeting of secreted ISGs may provide a benefit for patients after anti-PD-L 1 treatment failure. Expand