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Assistant Professor
My laboratory seeks to understand how innate differences (such as germline variants) in DNA replication and/or repair impact two critical areas in precision oncology: (1) what underlies an individual’s cancer risk, and (2) how an individual will respond to cancer treatment. Currently my work focuses on colorectal and renal tumors, but results from my work are applicable to multiple tumor types. My long-term goal is to increase our understanding of DNA replication, and repair pathways and their role in colorectal and other cancers, to better predict cancer risk and reduce cancer incidence by allowing opportunities to implement cancer prevention strategies and early detection.
Twitter: @sanjeevaniarora
Cancer genetic studies to improve screening, early detection and treatment
My laboratory seeks to understand how innate differences (such as germline variants) in DNA replication and/or repair impact two critical areas in precision oncology: (1) what underlies an individual’s cancer risk, and (2) how an individual will respond to cancer treatment. Currently my work focuses on colorectal and renal tumors, but results from my work are applicable to multiple tumor types.
In the area of cancer risk prediction, we seek to identify and functionally assess novel or rare ‘risk’ germline variants in the population. Knowing which germline variants confer risk and which don’t is important because physicians don’t know how to act upon the massive number of variants of uncertain significance that have been identified by sequencing studies. We currently are evaluating variants in replicative DNA polymerases, POLE and POLD1, as these are known to cause mutagenesis, genetic instability and cancer (such as colorectal, endometrial).
Our approach to solving the ‘too many uncertain variants’ problem is based on a novel hypothesis, that germline POLE and POLD1 variants that are dysfunctional in the tumor also have a detectable dysfunctional signature in the germline. We are leveraging big data of tumor and germline to build a Germline Signature, which can be adopted into clinical practice to guide risk prediction and allow for application of cancer prevention strategies (e.g., lifestyle interventions) or early detection (e.g. by improving cancer screening panels). Collaborating with clinical partners, we plan to improve and validate this tool in prospective studies. Longer term, we plan to use the Germline Signature to build risk prediction models.
In the area of individual response to cancer treatment, we are integrating germline variation data with biological assessment of innate capacity to repair DNA damage to develop a ‘signature’ that predicts the magnitude of benefit from chemoradiation therapy. My approach is particularly novel because tumor-specific signatures have been sought but no biomarker has ever been established; this may be because prior studies did not evaluate innate factors. This work will deliver preclinical evidence that could allow for precision stratification of patients to therapies.
Currently, my two research directions are relatively separate. But I envision they will eventually meet. By pursuing both it may be possible to identify specific innate factors that influence both risk and response to treatment. Results may elucidate mechanisms common to many cancers and/or underlying predisposition to a certain tumor type.
In the area of cancer risk prediction, we seek to identify and functionally assess novel or rare ‘risk’ germline variants in the population. Knowing which germline variants confer risk and which don’t is important because physicians don’t know how to act upon the massive number of variants of uncertain significance that have been identified by sequencing studies. We are evaluating genetic variants in replicative DNA polymerases, POLE and POLD1, as these are known to cause mutagenesis, genetic instability and cancer (such as colorectal, endometrial).
Our approach to solving the ‘too many variants of uncertain significance’ problem is based on a novel hypothesis, that germline POLE and POLD1 variants that are dysfunctional in the tumor also have a detectable dysfunctional signature in the germline. We are leveraging big data of tumor and germline to build a Germline Signature, which can be adopted into clinical practice to guide risk prediction and allow for application of cancer prevention strategies (e.g., lifestyle interventions) or early detection (e.g. by improving cancer screening panels). Collaborating with clinical partners, we plan to improve and validate this tool in prospective studies. Longer term, we plan to use the Germline Signature to build risk prediction models.
In the area of cancer treatment, we are investigating biomarkers of therapeutic response in rectal cancer. Neoadjuvant chemoradiation therapy (nCRT) is currently the standard treatment for locally advanced rectal cancer (clinical TNM stage II—III). Locally advanced rectal cancer accounts for ~60% of newly diagnosed patients. For many patients, nCRT has dramatically improved outcomes, but ~70-80% of patients who receive nCRT show poor or no response, and CRT is extremely toxic. Currently, there is no clinically actionable biomarker to predict which rectal cancer patients are likely to respond to nCRT. As a result, many patients are exposed to this toxic, DNA damaging therapy (radiation and chemotherapy) without benefit. Therefore, a biomarker for nCRT response would improve precision treatment, and ultimately improve survival and prevent recurrence in individual with rectal cancer.
In the area of individual response to cancer treatment, we are integrating germline variation data with biological assessment of innate capacity to repair DNA damage to develop a ‘signature’ that predicts the magnitude of benefit from chemoradiation therapy. Our approach is particularly novel because tumor-specific signatures have been sought but no biomarker has ever been established; this may be because prior studies did not evaluate innate factors. This work will deliver preclinical evidence that could allow for precision stratification of patients to therapies.
Currently, my two research directions are relatively separate. But I envision they will eventually meet. By pursuing both it may be possible to identify specific innate factors that influence both risk and response to treatment. Results may elucidate mechanisms common to many cancers and/or underlying predisposition to a certain tumor type.
Jessica Mauricette, University of Delaware-FCCC Summer Fellow 2019
Current: Undergraduate student, University of Delaware
Randy Lesh, Alpha Omega Alpha Carolyn L. Kuckein Student Fellow 2019
Current: Medical student, Geisinger Commonwealth School of Medicine
Mercedes Davis, Drexel University Undergraduate Co-op
Current: Continuing undergraduate studies, Drexel University
Amanda Browne, NCI CURE Program Fellow
Current: Scientific Technician I, Arora Lab
Waleed Iqbal, Master’s thesis, Drexel University School of Medicine
Current: Graduate Student, School of Biomedical Engineering Science & Health Systems, Drexel University
Nina Shah, Summer Research Volunteer
Current: Continuing undergraduate studies, Haverford College
Hartman TR, Demidova EV, Lesh RW, Hoang L, Richardson M, Forman A, Kessler L, Speare S, Golemis EA, Hall MJ, Daly MB, Arora S*. Prevalence of pathogenic variants in DNA damage response and repair genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer. *Corresponding. Sci Rep. 2020 Aug 11;10(1):13518. doi: 10.1038/s41598-020-70449-5. PMID: 32782288
Arora S*, Velichinskii R, Lesh RW, Usman A, Kubiak M, Bansal P, Edelman MJ, Borghaei H, and Boumber Y*. Existing and emerging biomarkers for immune checkpoint immunotherapy in solid tumors. *Co-corresponding. Adv Ther. 2019 Aug 13. doi: 10.1007/s12325-019-01051-z. [Epub ahead of print] Review. PMID: 31410780
Nicolas E., Demidova E.V., Iqbal W., Serebriiskii I.G., Vlasenkova R., Ghatalia P., Zhou Y., Rainey K., Forman A.F., Dunbrack R.L., Jr., Golemis E.A., Hall M.J., Daly M.B., Arora S., Interaction of germline variants in a family with a history of early-onset clear cell renal cell carcinoma. Mol Genet Genomic Med. 7(3): e556, 2019. PMC6418363. 9.924
Serebriiskii I.G., Connelly C., Frampton G., Newberg J., Cooke M., Miller V., Ali S., Ross J.S., Handorf E., Arora S., Lieu C., Golemis E.A., Meyer J.E., Comprehensive characterization of ras mutations in colon and rectal cancers in old and young patients. Nat Commun. 10(1): 3722, 2019. PMC6700103. 11.878
Arora S., Heyza J.R., Chalfin E.C., Ruch R.J. ,Patrick S.M., Gap junction intercellular communication positively regulates cisplatin toxicity by inducing DNA damage through bystander signaling. Cancers (Basel). 10(10)2018. PMC6210410. 6.162
Arora S., Huwe P.J., Sikder R., Shah M., Browne A.J., Lesh R., Nicolas E., Deshpande S., Hall M.J., Dunbrack R.L., Jr., Golemis E.A., Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods. Cancer Biol Ther. 18(7): 519-533, 2017. PMC5639829. 2.879
Nicolas E, Golemis EA, Arora S*. POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies. Gene 590:128-41, 2016. Pubmed PMID: 27320729 *corresponding.
Nicolas E, Arora S, Zhou Y, Serebriiskii IG, Andrake MD, Handorf E, Bodia DL, Vockley JG, Dunbrack RL, Ross EA, Hall MJ, Golemis EA, Giri VN, and Daly MB. Systematic evaluation of underlying defects in DNA repair as an approach to case-only assessment of familial prostate cancer. Oncotarget 6:39614-33, 2015, PubMed PMID: 26485759. PMCID: 4741850
Arora S, Yan H, Cho I, Fan HY, Luo B, Gai X, Bodian DL, Vockley JG, Zhou Y, Handorf E, Egleston BL, Andrake M, Nicolas E, Serebriiskii I, Yen TJ, Hall MJ, Golemis EA, Enders GH. Genetic Variants That Predispose to DNA Double-strand Breaks in Lymphocytes from a Subset of Patients With Familial Colorectal Carcinomas. Gastroenterology 149:1872-1883, 2015. PMID: 26344056; PMCID: PMC4663158.
Arora S, Kothandapani A, Tillison K, Kalman-Maltese V, Patrick SM. Downregulation of XPF-ERCC1 enhances cisplatin efficacy in cancer cells. DNA Repair (Amst). 2010 Jul 1;9(7):745-53. PubMed PMID: 20418188; PubMed Central PMCID: PMC4331052.
Sanjeevani.Arora@fccc.edu
Office phone number: 215-214-3956
Office fax number: 215-728-4333
Lab phone number: 215-214-3964 and 3966
Office location: P2145B
Lab location: P2149
Sanjeevani.Arora@fccc.edu
Office phone number: 215-214-3956
Office fax number: 215-728-4333
Lab phone number: 215-214-3964 and 3966
Office location: P2145B
Lab location: P2149
Assistant Professor
My laboratory seeks to understand how innate differences (such as germline variants) in DNA replication and/or repair impact two critical areas in precision oncology: (1) what underlies an individual’s cancer risk, and (2) how an individual will respond to cancer treatment. Currently my work focuses on colorectal and renal tumors, but results from my work are applicable to multiple tumor types. My long-term goal is to increase our understanding of DNA replication, and repair pathways and their role in colorectal and other cancers, to better predict cancer risk and reduce cancer incidence by allowing opportunities to implement cancer prevention strategies and early detection.
Twitter: @sanjeevaniarora
Cancer genetic studies to improve screening, early detection and treatment
My laboratory seeks to understand how innate differences (such as germline variants) in DNA replication and/or repair impact two critical areas in precision oncology: (1) what underlies an individual’s cancer risk, and (2) how an individual will respond to cancer treatment. Currently my work focuses on colorectal and renal tumors, but results from my work are applicable to multiple tumor types.
In the area of cancer risk prediction, we seek to identify and functionally assess novel or rare ‘risk’ germline variants in the population. Knowing which germline variants confer risk and which don’t is important because physicians don’t know how to act upon the massive number of variants of uncertain significance that have been identified by sequencing studies. We currently are evaluating variants in replicative DNA polymerases, POLE and POLD1, as these are known to cause mutagenesis, genetic instability and cancer (such as colorectal, endometrial).
Our approach to solving the ‘too many uncertain variants’ problem is based on a novel hypothesis, that germline POLE and POLD1 variants that are dysfunctional in the tumor also have a detectable dysfunctional signature in the germline. We are leveraging big data of tumor and germline to build a Germline Signature, which can be adopted into clinical practice to guide risk prediction and allow for application of cancer prevention strategies (e.g., lifestyle interventions) or early detection (e.g. by improving cancer screening panels). Collaborating with clinical partners, we plan to improve and validate this tool in prospective studies. Longer term, we plan to use the Germline Signature to build risk prediction models.
In the area of individual response to cancer treatment, we are integrating germline variation data with biological assessment of innate capacity to repair DNA damage to develop a ‘signature’ that predicts the magnitude of benefit from chemoradiation therapy. My approach is particularly novel because tumor-specific signatures have been sought but no biomarker has ever been established; this may be because prior studies did not evaluate innate factors. This work will deliver preclinical evidence that could allow for precision stratification of patients to therapies.
Currently, my two research directions are relatively separate. But I envision they will eventually meet. By pursuing both it may be possible to identify specific innate factors that influence both risk and response to treatment. Results may elucidate mechanisms common to many cancers and/or underlying predisposition to a certain tumor type.
In the area of cancer risk prediction, we seek to identify and functionally assess novel or rare ‘risk’ germline variants in the population. Knowing which germline variants confer risk and which don’t is important because physicians don’t know how to act upon the massive number of variants of uncertain significance that have been identified by sequencing studies. We are evaluating genetic variants in replicative DNA polymerases, POLE and POLD1, as these are known to cause mutagenesis, genetic instability and cancer (such as colorectal, endometrial).
Our approach to solving the ‘too many variants of uncertain significance’ problem is based on a novel hypothesis, that germline POLE and POLD1 variants that are dysfunctional in the tumor also have a detectable dysfunctional signature in the germline. We are leveraging big data of tumor and germline to build a Germline Signature, which can be adopted into clinical practice to guide risk prediction and allow for application of cancer prevention strategies (e.g., lifestyle interventions) or early detection (e.g. by improving cancer screening panels). Collaborating with clinical partners, we plan to improve and validate this tool in prospective studies. Longer term, we plan to use the Germline Signature to build risk prediction models.
In the area of cancer treatment, we are investigating biomarkers of therapeutic response in rectal cancer. Neoadjuvant chemoradiation therapy (nCRT) is currently the standard treatment for locally advanced rectal cancer (clinical TNM stage II—III). Locally advanced rectal cancer accounts for ~60% of newly diagnosed patients. For many patients, nCRT has dramatically improved outcomes, but ~70-80% of patients who receive nCRT show poor or no response, and CRT is extremely toxic. Currently, there is no clinically actionable biomarker to predict which rectal cancer patients are likely to respond to nCRT. As a result, many patients are exposed to this toxic, DNA damaging therapy (radiation and chemotherapy) without benefit. Therefore, a biomarker for nCRT response would improve precision treatment, and ultimately improve survival and prevent recurrence in individual with rectal cancer.
In the area of individual response to cancer treatment, we are integrating germline variation data with biological assessment of innate capacity to repair DNA damage to develop a ‘signature’ that predicts the magnitude of benefit from chemoradiation therapy. Our approach is particularly novel because tumor-specific signatures have been sought but no biomarker has ever been established; this may be because prior studies did not evaluate innate factors. This work will deliver preclinical evidence that could allow for precision stratification of patients to therapies.
Currently, my two research directions are relatively separate. But I envision they will eventually meet. By pursuing both it may be possible to identify specific innate factors that influence both risk and response to treatment. Results may elucidate mechanisms common to many cancers and/or underlying predisposition to a certain tumor type.
Jessica Mauricette, University of Delaware-FCCC Summer Fellow 2019
Current: Undergraduate student, University of Delaware
Randy Lesh, Alpha Omega Alpha Carolyn L. Kuckein Student Fellow 2019
Current: Medical student, Geisinger Commonwealth School of Medicine
Mercedes Davis, Drexel University Undergraduate Co-op
Current: Continuing undergraduate studies, Drexel University
Amanda Browne, NCI CURE Program Fellow
Current: Scientific Technician I, Arora Lab
Waleed Iqbal, Master’s thesis, Drexel University School of Medicine
Current: Graduate Student, School of Biomedical Engineering Science & Health Systems, Drexel University
Nina Shah, Summer Research Volunteer
Current: Continuing undergraduate studies, Haverford College
Hartman TR, Demidova EV, Lesh RW, Hoang L, Richardson M, Forman A, Kessler L, Speare S, Golemis EA, Hall MJ, Daly MB, Arora S*. Prevalence of pathogenic variants in DNA damage response and repair genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer. *Corresponding. Sci Rep. 2020 Aug 11;10(1):13518. doi: 10.1038/s41598-020-70449-5. PMID: 32782288
Arora S*, Velichinskii R, Lesh RW, Usman A, Kubiak M, Bansal P, Edelman MJ, Borghaei H, and Boumber Y*. Existing and emerging biomarkers for immune checkpoint immunotherapy in solid tumors. *Co-corresponding. Adv Ther. 2019 Aug 13. doi: 10.1007/s12325-019-01051-z. [Epub ahead of print] Review. PMID: 31410780
Nicolas E., Demidova E.V., Iqbal W., Serebriiskii I.G., Vlasenkova R., Ghatalia P., Zhou Y., Rainey K., Forman A.F., Dunbrack R.L., Jr., Golemis E.A., Hall M.J., Daly M.B., Arora S., Interaction of germline variants in a family with a history of early-onset clear cell renal cell carcinoma. Mol Genet Genomic Med. 7(3): e556, 2019. PMC6418363. 9.924
Serebriiskii I.G., Connelly C., Frampton G., Newberg J., Cooke M., Miller V., Ali S., Ross J.S., Handorf E., Arora S., Lieu C., Golemis E.A., Meyer J.E., Comprehensive characterization of ras mutations in colon and rectal cancers in old and young patients. Nat Commun. 10(1): 3722, 2019. PMC6700103. 11.878
Arora S., Heyza J.R., Chalfin E.C., Ruch R.J. ,Patrick S.M., Gap junction intercellular communication positively regulates cisplatin toxicity by inducing DNA damage through bystander signaling. Cancers (Basel). 10(10)2018. PMC6210410. 6.162
Arora S., Huwe P.J., Sikder R., Shah M., Browne A.J., Lesh R., Nicolas E., Deshpande S., Hall M.J., Dunbrack R.L., Jr., Golemis E.A., Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods. Cancer Biol Ther. 18(7): 519-533, 2017. PMC5639829. 2.879
Nicolas E, Golemis EA, Arora S*. POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies. Gene 590:128-41, 2016. Pubmed PMID: 27320729 *corresponding.
Nicolas E, Arora S, Zhou Y, Serebriiskii IG, Andrake MD, Handorf E, Bodia DL, Vockley JG, Dunbrack RL, Ross EA, Hall MJ, Golemis EA, Giri VN, and Daly MB. Systematic evaluation of underlying defects in DNA repair as an approach to case-only assessment of familial prostate cancer. Oncotarget 6:39614-33, 2015, PubMed PMID: 26485759. PMCID: 4741850
Arora S, Yan H, Cho I, Fan HY, Luo B, Gai X, Bodian DL, Vockley JG, Zhou Y, Handorf E, Egleston BL, Andrake M, Nicolas E, Serebriiskii I, Yen TJ, Hall MJ, Golemis EA, Enders GH. Genetic Variants That Predispose to DNA Double-strand Breaks in Lymphocytes from a Subset of Patients With Familial Colorectal Carcinomas. Gastroenterology 149:1872-1883, 2015. PMID: 26344056; PMCID: PMC4663158.
Arora S, Kothandapani A, Tillison K, Kalman-Maltese V, Patrick SM. Downregulation of XPF-ERCC1 enhances cisplatin efficacy in cancer cells. DNA Repair (Amst). 2010 Jul 1;9(7):745-53. PubMed PMID: 20418188; PubMed Central PMCID: PMC4331052.
This Fox Chase professor participates in the Undergraduate Summer Research Fellowship.
Learn more about Research Volunteering.