PBRM1 is the second most commonly mutated gene in clear cell renal cell carcinoma (the most common type of kidney cancer) and was first identified in 2011. Despite this, little is known about what the role of PBRM1 loss is in kidney cancer. We are currently exploring changes in chromatin modification that occur after it is lost and identifying potential avenues for personalized treatment strategies in advance cases of kidney cancer.
When patients have muscle-invasive bladder cancer, the standard of care is to be treated with cisplatin-based chemotherapy before surgery to remove the entire bladder. At the time of bladder removal, about 30-40% of patients will not have residual cancer left in their bladder. Patients and doctors alike wonder if bladder removal is necessary if there is no tumor left. The answer at this point in time is “yes” because we do not have a way to reliably identify patients who will respond to chemotherapy (prospectively), or patients who actually did respond to chemotherapy (retrospectively). We are currently using next generation sequencing to prospectively and retrospectively identify responders, with the aim to safely avoid bladder removal in responders in the future.
Lastly, bladder cancer sequencing efforts have revealed a large number of potentially therapeutically tractable targets, but how to target them is still unknown. These genetic alterations can be modeled in mice using the exciting new genome editing tool CRISPR. Using this technology, we are making many new bladder cancer models by introducing combinations of mutations into the mouse bladder to try to model the human disease more accurately in mice. This will hopefully allow us to marry individual mutations to therapeutic strategies in anticipation of personalized medicine algorithms in humans.
Stromyer M.L., Southerland M.R., Satyal U., Sikder R.K., Weader D.J., Baughman J.A., Youngs W.J., Abbosh P.H., Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines. Eur J Med Chem. 185: 111832, 2020. 4.833 PubMed
Li Q, Damish AW, Frazier Z, Liu D, Reznichenko E, Kamburov A, Bell A, Zhao H, Jordan EJ, Gao SP, Ma J, Abbosh PH, Bellmunt J, Plimack ER, Lazaro JB, Solit DB, Bajorin D, Rosenberg JE, D'Andrea AD, Riaz N, Van Allen EM, Iyer G, Mouw KW, ERCC2 Helicase Domain Mutations Confer Nucleotide Excision Repair Deficiency and Drive Cisplatin Sensitivity in Muscle-Invasive Bladder Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2019; 25(3):977-988. NIHMSID: NIHMS1016538 PubMed [journal] PMID: 29980530, PMCID: PMC6434536
Abbosh P., Sundararajan S., Millis S.Z., Hauben A., Reddy S., Geynisman D.M.,Uzzo R., Molecular and genomic profiling to identify actionable targets in chromophobe renal cell cancer. Eur Urol Focus. 4(6): 969-971, 2018. PubMed
Geynisman D.M., Abbosh P.H., Plimack E.R.,Zibelman M., Chemoimmunotherapy in metastatic urothelial carcinoma. Eur Urol. 73(5): 760-762, 2018. Editorial. 17.298
Hernandez Borrero L.J., Sikder R., Lulla A., Gokare P., Del Valle P.R., Tian X., Zhang S., Abbosh P.H.,El-Deiry W.S., Bcl-2 protein targeting by the p53/p21 complex-letter. Cancer Res. 78(10): 2770-2771, 2018. Letter. 8.378
Liu D., Abbosh P., Keliher D., Reardon B., Miao D., Mouw K., Weiner-Taylor A., Wankowicz S., Han G., Teo M.Y., Cipolla C., Kim J., Iyer G., Al-Ahmadie H., Dulaimi E., Chen D.Y.T., Alpaugh R.K., Hoffman-Censits J., Garraway L.A., Getz G., Carter S.L., Bellmunt J., Plimack E.R., Rosenberg J.E.,Van Allen E.M., Mutational patterns in chemotherapy resistant muscle-invasive bladder cancer. Nat Commun. 8(1): 2193, 2017. PMC5736752. 11.878 PMCID: PMC5736752
McIntosh A.G., Li T., Ito T., Mannion J., Dziemianowicz M., Waingankar N., Haseebuddin M., Chen D.Y.T., Greenberg R.E., Viterbo R., Kutikov A., Uzzo R.G., Smaldone M.C.,Abbosh P.H., Wbc associates with readmission following cystectomy. Bladder Cancer. 3(2): 95-103, 2017. PMC5409152.
Philip.Abbosh@fccc.edu
Office: 215-214-4212
Lab: 215-214-4295
Office: P2047
Philip.Abbosh@fccc.edu
Office: 215-214-4212
Lab: 215-214-4295
Office: P2047
Assistant Professor
Twitter: @scientistatlrge
PBRM1 is the second most commonly mutated gene in clear cell renal cell carcinoma (the most common type of kidney cancer) and was first identified in 2011. Despite this, little is known about what the role of PBRM1 loss is in kidney cancer. We are currently exploring changes in chromatin modification that occur after it is lost and identifying potential avenues for personalized treatment strategies in advance cases of kidney cancer.
When patients have muscle-invasive bladder cancer, the standard of care is to be treated with cisplatin-based chemotherapy before surgery to remove the entire bladder. At the time of bladder removal, about 30-40% of patients will not have residual cancer left in their bladder. Patients and doctors alike wonder if bladder removal is necessary if there is no tumor left. The answer at this point in time is “yes” because we do not have a way to reliably identify patients who will respond to chemotherapy (prospectively), or patients who actually did respond to chemotherapy (retrospectively). We are currently using next generation sequencing to prospectively and retrospectively identify responders, with the aim to safely avoid bladder removal in responders in the future.
Lastly, bladder cancer sequencing efforts have revealed a large number of potentially therapeutically tractable targets, but how to target them is still unknown. These genetic alterations can be modeled in mice using the exciting new genome editing tool CRISPR. Using this technology, we are making many new bladder cancer models by introducing combinations of mutations into the mouse bladder to try to model the human disease more accurately in mice. This will hopefully allow us to marry individual mutations to therapeutic strategies in anticipation of personalized medicine algorithms in humans.
Stromyer M.L., Southerland M.R., Satyal U., Sikder R.K., Weader D.J., Baughman J.A., Youngs W.J., Abbosh P.H., Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines. Eur J Med Chem. 185: 111832, 2020. 4.833 PubMed
Li Q, Damish AW, Frazier Z, Liu D, Reznichenko E, Kamburov A, Bell A, Zhao H, Jordan EJ, Gao SP, Ma J, Abbosh PH, Bellmunt J, Plimack ER, Lazaro JB, Solit DB, Bajorin D, Rosenberg JE, D'Andrea AD, Riaz N, Van Allen EM, Iyer G, Mouw KW, ERCC2 Helicase Domain Mutations Confer Nucleotide Excision Repair Deficiency and Drive Cisplatin Sensitivity in Muscle-Invasive Bladder Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2019; 25(3):977-988. NIHMSID: NIHMS1016538 PubMed [journal] PMID: 29980530, PMCID: PMC6434536
Abbosh P., Sundararajan S., Millis S.Z., Hauben A., Reddy S., Geynisman D.M.,Uzzo R., Molecular and genomic profiling to identify actionable targets in chromophobe renal cell cancer. Eur Urol Focus. 4(6): 969-971, 2018. PubMed
Geynisman D.M., Abbosh P.H., Plimack E.R.,Zibelman M., Chemoimmunotherapy in metastatic urothelial carcinoma. Eur Urol. 73(5): 760-762, 2018. Editorial. 17.298
Hernandez Borrero L.J., Sikder R., Lulla A., Gokare P., Del Valle P.R., Tian X., Zhang S., Abbosh P.H.,El-Deiry W.S., Bcl-2 protein targeting by the p53/p21 complex-letter. Cancer Res. 78(10): 2770-2771, 2018. Letter. 8.378
Liu D., Abbosh P., Keliher D., Reardon B., Miao D., Mouw K., Weiner-Taylor A., Wankowicz S., Han G., Teo M.Y., Cipolla C., Kim J., Iyer G., Al-Ahmadie H., Dulaimi E., Chen D.Y.T., Alpaugh R.K., Hoffman-Censits J., Garraway L.A., Getz G., Carter S.L., Bellmunt J., Plimack E.R., Rosenberg J.E.,Van Allen E.M., Mutational patterns in chemotherapy resistant muscle-invasive bladder cancer. Nat Commun. 8(1): 2193, 2017. PMC5736752. 11.878 PMCID: PMC5736752
McIntosh A.G., Li T., Ito T., Mannion J., Dziemianowicz M., Waingankar N., Haseebuddin M., Chen D.Y.T., Greenberg R.E., Viterbo R., Kutikov A., Uzzo R.G., Smaldone M.C.,Abbosh P.H., Wbc associates with readmission following cystectomy. Bladder Cancer. 3(2): 95-103, 2017. PMC5409152.
This Fox Chase professor participates in the Undergraduate Summer Research Fellowship.
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