Ebos Lab Research: Drug Side Effects

Treatment-induced secretomes

Our lab studies a common drug side effect that includes the secretion of proteins. Treatment-induced secretomes (therasomes) are activated by antiangiogenic and immune checkpoint inhibitors and can be exploited as biomarkers of treatment efficacy, drug dosing and predict patient relapse.

Key papers

• Shi Y, et al. Acquired resistance to PD-L1 inhibition is associated with an enhanced type I IFN-stimulated secretory program in tumor cells. bioRxiv 2021.07.01.450417. doi.org/10.1101/2021.07.01.450417.
• Mastri M, et al. Tumor-Independent Host Secretomes Induced By Angiogenesis and Immune-Checkpoint Inhibitors. Mol Cancer Ther. 2018 Jul;17(7):1602-1612. doi: 10.1158/1535-7163.MCT-17-1066.
• Ebos JM, Kerbel RS. Antiangiogenic therapy: impact on invasion, disease progression, and metastasis. Nat Rev Clin Oncol. 2011 Mar 1;8(4):210-21. doi: 10.1038/nrclinonc.2011.21.

Senescence-mimicking drugs

Senescence is a form of cellular aging that can be induced by many cancer drugs. Our lab has discovered that antiangiogenic TKIs can induce a senescence-mimicking effect (senomimetic) which can drive the secretion of proteins that fuel tumor-promoting programs and resistance.

Our recent work demonstrates that senomimetic drug side effects can also activate immune-modulating signaling that can “prime” tumors for better responses to immune checkpoint inhibition.

Key papers

• Dolan, et al. A senescence-mimicking (senomimetic) VEGFR TKI side-effect primes tumor immune responses via IFN/STING signaling. Mol. Can. Ther. 2024 (in press). doi: 10.1158/1535-7163.MCT-24-0139
• Mastri M, et al. A Transient Pseudosenescent Secretome Promotes Tumor Growth after Antiangiogenic Therapy Withdrawal. Cell Rep. 2018 Dec 26;25(13):3706-3720.e8. doi: 10.1016/j.celrep.2018.12.017. PMID: 30590043.
• Mastri M, Ebos JML. Tumor growth fueled by spurious senescence phenotypes. Mol Cell Oncol. 2019 Feb 20;6(2):1575707. doi: 10.1080/23723556.2019.1575707.