Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond.
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2018-01-25
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Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.
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Zhu, Jason, Andrew J Armstrong, Terence W Friedlander, Won Kim, Sumanta K Pal, Daniel J George and Tian Zhang (2018). Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond. J Immunother Cancer, 6(1). p. 4. 10.1186/s40425-018-0314-1 Retrieved from https://hdl.handle.net/10161/16029.
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Andrew John Armstrong
I am a clinical and translational investigator focused on precision therapies and biomarkers in advanced prostate and other GU cancers. I oversee a large research team of clinical and lab based investigators focused on improving patient outcomes, preventing metastatic disease, and understanding the biology of aggressive prostate cancer. Some key themes:
1. Predictors of sensitivity and clinical efficacy of therapies in advanced prostate cancer
2. Novel designs of clinical trials and pharmacodynamic/translational studies in prostate, kidney, bladder cancer
3. Pre-operative models for drug development of novel agents in human testing in prostate cancer
4. Novel therapies and drug development for prostate, renal, bladder, and testicular cancer
5. Design of rational combination therapies in men with metastatic hormone-refractory prostate cancer
6. Developing prognostic and predictive models for progression and survival in metastatic prostate cancer
7. Examining surrogate markers of mortality in metastatic prostate cancer
8. Clear cell and non-clear cell renal cell carcinoma: natural history, sensitivity to novel agents including mTOR and VEGF inhibition
Daniel James George
Tian Zhang
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