Sanjeevani Arora, PhD

Sanjeevani Arora, PhD

This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
Learn more about Research Volunteering.

Assistant Professor

Member, Cancer Epigenetics Institute

Lab Overview

My Lab's core affiliation is with the Cancer Prevention and Control Program at FCCC. In addition, I hold an adjunct position in the Department of Radiation Oncology, am a member of the Cancer Epigenetics Institute within FCCC and maintain adjunct faculty roles at Drexel University School of Medicine, Temple University’s Lewis Katz School of Medicine, and its College of Public Health

My principal focus revolves around understanding how innate genetic variation in DNA repair can shape an individual's predisposition to cancer and influence the outcomes for patients undergoing DNA-damaging treatments, such as chemotherapy and radiation. As a trained molecular geneticist, I delve into studying polymorphisms or mutations that may compromise the efficiency of DNA damage response and repair. With this knowledge, our goal is to identify biomarkers that can predict cancer susceptibility and treatment outcomes. These potential biomarkers include unique genes, their polymorphisms, proteins, and other molecular signifiers that shed light on both cancer risks and patient outcomes. In my lab, we adopt a multi-disciplinary approach, harnessing techniques from molecular genetics, biochemistry, and cellular biology. We actively collaborate with a diverse group of professionals, including clinicians, epidemiologists, bioinformaticians, and computational biologists.

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    DNA damage response and repair marker (gammaH2AX) significantly segregates early-onset colorectal cancer patients from matched cancer-free controls. GammaH2AX marker was assessed in peripheral blood lymphocytes of familial early-onset colorectal cancer patients and matched controls (Figure from Arora et. al., Gastroenterology 2015).

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    POLE and POLD1 are the major replicative DNA polymerases. Genetic mutations in POLE and POLD1 lead to proofreading errors occur throughout the genome, causing mutagenesis, genetic instability and cancer. The cancer spectrum of POLE and POLD1 includes colorectal, endometrial and other tumors. (Figure from Nicolas et. al., Gene 2016).

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    Early-onset renal cancer (eoRC) patients carry germline pathogenic variants in DNA damage response and repair genes These results indicate that patients diagnosed with eoRC may benefit from undergoing comprehensive multigene panel testing that includes genes outside of the scope of those currently known to increase renal cancer risk. (Figure from Hartman et. al., Scientific Reports 2020).

    Clinical

    Educational Background

    • Postdoctoral Fellow, Fox Chase Cancer Center, Philadelphia, PA, 2017
    • PhD, University of Toledo - Health Science Campus, Toledo, OH, 2012
    • MS, CMR Institute of Management Studies, Bangalore University, Bangalore, India, 2006
    • BS, Garden City College, Bangalore University, Bangalore, Karnataka, 2004

    Certifications

    • AACR Integrative Molecular Epidemiology: Bridging Cancer Biology and Precision Medicine, July 2017
    • ACMG Genomics Case Conference: "Solving the Unresolved: A systematic approach to WES Negative Patients in the Undiagnosed Diseases Network"

    Memberships

    • Co-Leader, Colorectal Cancer Genetics & Genomics Group, African Caribbean Cancer Consortium
    • GI Malignancy Working Group, NCI Radiation Research Program
    • Collaborative Group of Americas on Inherited Gastrointestinal Cancer (CGA- IGC)
    • Chair, Research Committee, CGA-IGC
    • Active Member, American Association for Cancer Research
    • Coalition Member, Genetics/Genomics Working Group, PA Cancer Coalition

    Honors & Awards

    • CPC Pilot Award, Fox Chase Cancer Center (PI: Arora), 2024
    • Multi-PI Pilot Award, Fox Chase Cancer Center (PI: Arora, Taylor-Wilson), 2022
    • Multi-PI Pilot Award, Fox Chase Cancer Center (PI: Arora, Meyer), 2022
    • Career Enhancement Program Award, Yale Head and Neck Cancer SPORE, 2021-2022
    • FY17 Peer Reviewed  Cancer Research Program (PRCRP) Career Development Award, 2018
    • NCI T32 training fellowship, 2016
    • Travel award for presenting at “ACMG Annual Clinical Genetics meeting” in Salt Lake City, UT, Fox Chase Cancer Center Postdoctoral program, 2015
    •  1st place- Oral presentation, 19th Annual Postdoctoral Day, Fox Chase Cancer Center, 2014
    •  "Board of Directors" Postdoctoral Fellowship, Fox Chase Cancer Center 2013

     

     

    Find the Fox Chase Cancer Center Trainee Association on LinkedIn

     

          BlueSky:: @sanjeevani-arora.bsky.social

     

     

     

     

     

     

    People

    Additional Staff

    Demitrios Dedousis, MD 
    Hematology-Oncology Fellow 
     

    Jasmeet Kaur, MD 
    Hematology-Oncology Fellow 
     

    Zachary Kiss, DO 
    Radiation Oncology Resident 
     

    Former Personnel:

    Elena Demidova
    Doctoral Thesis Advisor 
    FCCC-Russian State Medical University Sister Institute Program 
    Current: GMP Manufacturing Associate, Clinical Vector Core, Raymond G. Perelman Center for Cellular, UPenn

    Tiffiney R. Hartman, Ph.D. 
    Thesis Advisor, Arcadia University, PA 
    Current: Genetic Counselor, Roberts Individualized Medical Genetics Center, and the Division of Human Genetics at Children's Hospital of Philadelphia and Associate Director Genetic Counseling Certificate Program, UPenn

    Shreya Shah, B.S., Research Assistant 
    Current: M2, University of Maryland School of Medicine

    Jessica Mauricette, University of Delaware-FCCC Summer Fellow 2019 
    Current:Medical Student, Drexel University College of Medicine

    Randy Lesh, Alpha Omega Alpha Carolyn L. Kuckein Student Fellow 2019 
    Current: Resident Physician, Head and Neck surgery, Geisinger

    Mercedes Davis, Drexel University Undergraduate Co-op 
    Current: Continuing undergraduate studies, Drexel University

    Amanda Browne, Scientific Technician I, Arora Lab  
    Current: Associate Scientist, GSK, Infectious Disease Research Unit

    Research Interests

    • Determinants of cancer risk 
    • Predictive biomarkers for response to cancer therapy 
    • Novel strategies to screen for individuals at high-risk for cancer

    Lab Description

    1. Variability in response to chemoradiation therapy. The ability of cells to recognize and repair DNA damage, particularly double-strand breaks (DSBs), is key to cell survival following chemoradiation therapy (CRT). We are investigating biological factors that influence DSB repair, which may explain the varied responses to CRT. This study is particularly relevant in locally advanced rectal cancer (LARC), where neoadjuvant CRT (nCRT) followed by surgery is the standard of care.
    In recent work, we have demonstrated that not all patients equally benefit from CRT in the setting of LARC. We found that Non-Hispanic Black patients receiving CRT respond significantly less favorably compared to Non-Hispanic White patients. we discovered that disparities in LARC treatment outcomes based on race/ethnicity are complex and multifaceted, influenced by various socioeconomic, clinical, and pathologic factors. However, even after accounting for these factors, Non-Hispanic Black patients still had significantly reduced benefit from CRT, suggesting the need to explore factors—such as biological—to address these disparities. This finding underscores a critical gap in our comprehension of CRT response and align with our ongoing research into the biological factors influencing CRT efficacy. Based on our findings, we aim to shed light on the biological underpinnings of racial/ethnic disparities in CRT responses in rectal cancer patients. My lab has secured funding from the Department of Defense and the National Institute of Health to support this work.

    2. Predictive biomarkers of response to chemoradiation therapy. Approximately 60% of newly diagnosed rectal cancer cases are locally advanced (i.e., LARC). All LARC patients get the standard of care, nCRT followed by surgery, however, not all patients derive complete benefit. This underscores a critical need for predictive biomarkers capable of discerning responders from poor responders.
    Using methods I developed during my postdoctoral fellowship, in my lab, I tested an innovative hypothesis positing that inherent variation in the expression of DNA damage response (DDR) proteins could predict benefit from CRT. Our primary focus is on validating assays for standardized detection of DDR proteins in minimally invasive human biospecimens, such as blood. My lab has secured a multi-phase NIH (NCI) UH2/UH3 award, equivalent to an NIH R01 grant, to support this translational project. Our goal is clinical validation of the DDR assay to the point where it can be integrated, in the future, into clinical trials for predicting CRT response and guiding patient selection.

    3. Genome instability and early-onset cancer risk. The rising incidence of early-onset cancers - diagnosed before age 50 - is a significant concern in the US and globally. In our FCCC catchment area, there is a significant rise in CRC and renal cell carcinomas. My lab is providing novel insights into genetic risk of cancer, and its implications for therapy. My lab has secured pilot funding for this work as we actively seek funding through other extramural sources.
     

    Selected Publications

    Shulman RM, Deng M, Handorf EA, Meyer JE, Lynch SM, Arora S. Factors Associated With Racial and Ethnic Disparities in Locally Advanced Rectal Cancer Outcomes. JAMA Netw Open. 2024 Feb 5;7(2):e240044. doi: 10.1001/jamanetworkopen.2024.0044.PMID: 38421650 

    Shah SM, Demidova EV, Ringenbach S, Faezov B, Andrake M, Gandhi A, Mur P, Viana-Errasti J, Xiu J, Swensen J, Valle L, Dunbrack RL Jr, Hall MJ, Arora S. Exploring Co-occurring POLE Exonuclease and Non-exonuclease Domain Mutations and Their Impact on Tumor Mutagenicity. Cancer Res Commun. 2024 Jan 26;4(1):213-225. doi: 10.1158/2767-9764.CRC-23-0312. Epub 2024 Jan 8. PMID: 38282550 

    Rodgers-Fouche L, Arora S, Ricker C, Li D, Farooqi M, Balaguer F, Dominguez-Valentin M, Guillem JG, Kanth P, Liska D, Melson J, Mraz KA, Shirts BH, Vilar E, Katona BW, Hodan R. Exploring Stakeholders' Perspectives on Implementing Universal Germline Testing for Colorectal Cancer: Findings From a Clinical Practice Survey. JCO Precis Oncol. 2023 Sep;7:e2300440. doi: 10.1200/PO.23.00440. PMID: 37897815

    Shah S.M., Demidova E.V., Lesh R.W., Hall M.J., Daly M.B., Meyer J.E., Edelman M.J., Arora S., Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology. Cancer Treat Rev. 104: 102337, 2022. PMC9016579 https://www.ncbi.nlm.nih.gov/pubmed/35051883.

    Iqbal W., Demidova E.V., Serrao S., ValizadehAslani T., Rosen G., Arora S., Rrm2b is frequently amplified across multiple tumor types: Implications for DNA repair, cellular survival, and cancer therapy. Front Genet. 12: 628758, 2021.PMC8045241. https://www.ncbi.nlm.nih.gov/pubmed/33868369.

    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

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    Additional Publications

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    This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
    Learn more about Research Volunteering.