Steven Patierno

Overview:

Patierno's current translational research interests are focused on the genomics molecular biology of cancer disparities, cancer biology, molecular pharmacology and targeted experimental therapeutics to control prostate, breast and lung tumor aggressiveness. He is an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis, which includes a broad spectrum of laboratory and population level research.   Patierno is also actively engaged in cancer health disparities and healthcare delivery research focused on patient navigation, survivorship, community-based interventions, mHealth, implementation sciences, cancer care economics, and policy.

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Professor in Family Medicine and Community Health

Family Medicine and Community Health
School of Medicine

Core Faculty Member, Duke-Margolis Center for Health Policy

Duke - Margolis Center For Health Policy
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1981

University of Connecticut

Ph.D. 1985

University of Texas Medical School, Houston

Postdoctoral Training, Norris Comprehensive Cancer

University of Southern California

Grants:

Identification of Genetic Determinates for Disparities in African American Patients with Non-Small Cell Lung Cancer

Administered By
Medicine, Medical Oncology
Awarded By
V Foundation for Cancer Research
Role
Significant Contributor
Start Date
End Date

Targeting RNA splicing in race-related aggressive and lethal prostate cancer

Administered By
Duke Cancer Institute
Awarded By
Prostate Cancer Foundation
Role
Principal Investigator
Start Date
End Date

PC150506: Small molecule targeting of RNA splice variants driving tumor aggressiveness

Administered By
Chemistry
Awarded By
United States Army Medical Research Acquisition Activity
Role
Collaborator
Start Date
End Date

2/2 NCCU-DUKE Cancer Disparities Translational Research Partnership

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Detection of Novel Alternative Splicing Biomarkers of Hypoxia in Breast and Lung Tumors

Administered By
Radiation Oncology
Awarded By
Rsna Research & Education Fund
Role
Mentor
Start Date
End Date

Publications:

Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk.

Limited efforts have been made in assessing the effect of genome-wide profiling of RNA splicing-related variation on lung cancer risk. In the present study, we first identified RNA splicing-related genetic variants linked to lung cancer in a genome-wide profiling analysis and then conducted a two-stage (discovery and replication) association study in populations of European ancestry. Discovery and validation were conducted sequentially with a total of 29,266 cases and 56,450 controls from both the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium as well as the OncoArray database. For those variants identified as significant in the two datasets, we further performed stratified analyses by smoking status and histological type and investigated their effects on gene expression and potential regulatory mechanisms. We identified three genetic variants significantly associated with lung cancer risk: rs329118 in JADE2 (P = 8.80E-09), rs2285521 in GGA2 (P = 4.43E-08), and rs198459 in MYRF (P = 1.60E-06). The combined effects of all three SNPs were more evident in lung squamous cell carcinomas (P = 1.81E-08, P = 6.21E-08, and P = 7.93E-04, respectively) than in lung adenocarcinomas and in ever smokers (P = 9.80E-05, P = 2.70E-04, and P = 2.90E-05, respectively) than in never smokers. Gene expression quantitative trait analysis suggested a role for the SNPs in regulating transcriptional expression of the corresponding target genes. In conclusion, we report that three RNA splicing-related genetic variants contribute to lung cancer susceptibility in European populations. However, additional validation is needed, and specific splicing mechanisms of the target genes underlying the observed associations also warrants further exploration.
Authors
Yang, W; Liu, H; Zhang, R; Freedman, JA; Han, Y; Hung, RJ; Brhane, Y; McLaughlin, J; Brennan, P; Bickeboeller, H; Rosenberger, A; Houlston, RS; Caporaso, NE; Landi, MT; Brueske, I; Risch, A; Christiani, DC; Amos, CI; Chen, X; Patierno, SR; Wei, Q
MLA Citation
Yang, Wenjun, et al. “Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk.Npj Precis Oncol, vol. 6, no. 1, June 2022, p. 48. Pubmed, doi:10.1038/s41698-022-00281-9.
URI
https://scholars.duke.edu/individual/pub1526275
PMID
35773316
Source
pubmed
Published In
Npj Precis Oncol
Volume
6
Published Date
Start Page
48
DOI
10.1038/s41698-022-00281-9

Environmental Factors

Direct causes of most individual human cancers will not be identifiable, but there is incontrovertible evidence that certain chemical agents, radiation, and biologic agents contribute to the overall incidence of cancer. A traditional paradigm has classified carcinogenic agents as environmental, lifestyle-related or occupational, but many agents exhibit a complex interplay between all three sources of exposure. A recent paradigm in environmental carcinogenesis-gene-environment interactions, a concept used to describe the complex interplay between individual or population genetics and responses to chemical agents-has also undergone an expansive transformation into a more contemporary understanding of the human “exposome.” The exposome is the cumulative lifelong burden of disease-contributing stressors including exogenous and endogenous agents of all types, as well as an individual’s “omics” profile (genomics, epigenomics, transcriptomics, proteomics, metabolomics), and microbiome. Another traditional model of environmental carcinogenesis, that of the classic sequential model of initiation, promotion, conversion, and progression, has evolved towards less linear models that no longer classify carcinogens as initiators or promoters per se. Instead, we seek to understand the contribution of chemical agents to the various hallmarks of cancer: genomic instability, resisting cell death, deregulating cellular energetics, sustaining proliferative signals, evading growth suppressors, avoiding immune destruction, enabling replicative immortality, promoting tumor inflammation, activating invasion and metastasis, and inducing angiogenesis. These evolving new thought paradigms hold promise for improved exposure monitoring, more accurate identification and earlier detection of disease-consequential exposures, and increasingly effective primary, secondary, and tertiary public health and clinical cancer prevention and interception measures.
Authors
MLA Citation
Patierno, S. R. “Environmental Factors.” Abeloff’s Clinical Oncology, 2019, pp. 139-153.e2. Scopus, doi:10.1016/B978-0-323-47674-4.00010-4.
URI
https://scholars.duke.edu/individual/pub1510024
Source
scopus
Published Date
Start Page
139
End Page
153.e2
DOI
10.1016/B978-0-323-47674-4.00010-4

Abstract D064: Race-related RNA splicing dysregulation of PI3Kd signaling: A therapeutic target for aggressive prostate cancer

<jats:title>Abstract</jats:title> <jats:p>Background: Age-adjusted incidence and mortality rates for prostate cancer (PCa) among African Americans (AAs) are greater than among whites. The more aggressive characteristics of PCa in AAs contribute to the disparity, in addition to social determinants of health. Prior work has shown race-related differential RNA splicing of PI3Kd in PCa tissue and a novel short RNA splice variant of PI3Kd enriched in PCa from AAs. This variant drives PCa aggressiveness and associates with poorer survival for PCa. PCa cells engineered to overexpress the PI3Kd variant enriched in PCa from AAs are resistant to CAL-101, a PI3Kd inhibitor, and those overexpressing the PI3Kd variant enriched in PCa from whites are sensitive to CAL-101. Available inhibitors that target race-related RNA splicing dysregulated pathways in PCa represent potential novel therapeutic strategies for aggressive PCa.</jats:p> <jats:p>Methods: We identified a panel of PI3Kd inhibitors of varying subunit specificity, which are available and/or currently being tested in other diseases. A panel of non-engineered PCa cell lines derived from AAs or whites were treated with the inhibitors and resulting alterations in proliferation were assessed using an Incucyte Live-Cell Imaging System. The cell lines were tested for baseline RNA and protein levels of total PI3K and levels of each PI3K subunit. After treatment, cells were tested for RNA levels of targets in pathways that cross talk with the PI3K pathway and downstream targets of PI3K signaling.</jats:p> <jats:p>Results: The seven non-engineered PCa cell lines derived from AAs or whites varied in PI3Kd subunit expression across a 60-fold range. A panel of seven PI3Kd inhibitors varied in subunit specificity for PI3Kd, with PI3Kg (lowly expressed) being the most common secondary target. Specificity for all other subunits ranged from 5-19,000x relative to PI3Kd IC50. LNCaP and LN95 cell lines had the highest baseline expression of PI3Kd and the largest inhibition of proliferation in response to the highly PI3Kd-specific inhibitors, parsaclisib and idelalisib, whereas 22RV1, MDA PCa 2b and VCaP cell lines had the lowest baseline expression of PI3Kd and the smallest response to the highly PI3Kd-specific inhibitors. However, none of the cell lines exhibited sensitivity to umbralisib, a highly PI3Kd-specific inhibitor, suggesting that subunit baseline expression is not the only factor determining sensitivity. All cell lines exhibited marked proliferation inhibition in response to copanlisib and LY3023414, which have less subunit specificity and/or known off-target effects. Further studies of effects of these inhibitors on oncogenic signaling and PCa cell biology are underway, including evaluation of inhibitor activity in PCa patient-derived xenografts derived from AAs or whites.</jats:p> <jats:p>Conclusions: PI3Kd inhibitors have a potential therapeutic role in PCa dependent on the PI3K subunit status of the tumor. PI3Kd inhibition has potential as a novel therapeutic strategy to improve outcomes for men with PCa driven by this mechanism.</jats:p> <jats:p>Citation Format: Bonnie L LaCroix, Daniel J George, Jennifer A Freedman, Steven R Patierno. Race-related RNA splicing dysregulation of PI3Kd signaling: A therapeutic target for aggressive prostate cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D064.</jats:p>
Authors
MLA Citation
LaCroix, Bonnie L., et al. “Abstract D064: Race-related RNA splicing dysregulation of PI3Kd signaling: A therapeutic target for aggressive prostate cancer.” Cancer Epidemiology, Biomarkers &Amp; Prevention, vol. 29, no. 6_Supplement_2, American Association for Cancer Research (AACR), 2020, pp. D064–D064. Crossref, doi:10.1158/1538-7755.disp19-d064.
URI
https://scholars.duke.edu/individual/pub1467298
Source
crossref
Published In
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Volume
29
Published Date
Start Page
D064
End Page
D064
DOI
10.1158/1538-7755.disp19-d064

Abstract A080: Rates of Invitation, participation, and willingness to engage in medical and clinical research: Findings from attendees at two gender-specific community-based screening programs

<jats:title>Abstract</jats:title> <jats:p>Introduction: Community-based screening programs are associated with increased access to care, particularly for traditionally underserved people of color, the poor, and those who face barriers to health care and resources. The utility of health fairs to increase access to care by providing screenings and services that include accountable and clearly articulated follow-up plans can, in part, address health disparities. Interestingly, the same populations that community-based screening programs typically serve are grossly under-represented in medical and clinical research, including biospecimen donation. Lack of diversity in medical and clinical research, including clinical trials and biobanking, has significant consequences, including lack of generalizability to broader diverse communities and limiting access to potentially life-saving and risk-reducing research.</jats:p> <jats:p>Methodology: Funded by the NCI (P30CA014236), the Duke Cancer Institute Office of Health Equity engaged community partners to conduct a population health assessment entitled Project PLACE (Population Level Approaches to Cancer Elimination). We collected 2,315 surveys of which 232 were respondents attending two gender-specific, community-based screening programs held in April 2017 and September 2017. We assessed access and participation in clinical research and biobanking, and likelihood to participate in medical research in the future among program attendees who completed the survey. We asked the following questions via self-administered pen and paper surveys: 1. Have you ever been asked to participate in a clinical trial or medical research? 2. Did you decide to participate in the clinical trial or medical research? 3. Have you ever been asked to donate bio specimens (blood, saliva, or other tissue) for the purpose of medical research? 4. Did you decide to donate the bio specimen? 5. How likely would you be to participate in medical research in the future?</jats:p> <jats:p>Results: Two-hundred and thirty-two (232) respondents completed the survey questions related to research participation. Thirty percent of respondents have been asked to participate in clinical research in the past, of whom 22% did participate. Twenty percent (22%) of respondents have been asked to donate bio specimens for research, of whom 16% have donated. Fifty percent (50%) of respondents report that they would or are likely to participate in medical research in the future.</jats:p> <jats:p>Conclusions: This study highlights community-based screening programs as a viable outlet to reach and engage participants in medical and clinical research. Of note, 50% of respondents who were primarily African American/Black are likely to participate in medical research in the future. Multiple factors including the longevity of the screening programs, and the quality of partnerships and engagement between the DCI and collaborating community organizations may also influence these outcomes.</jats:p> <jats:p>Citation Format: Kearston L. Ingraham, Joan Packenham, Demetrius Harvey, Steven Patierno, Nadine J. Barrett. Rates of Invitation, participation, and willingness to engage in medical and clinical research: Findings from attendees at two gender-specific community-based screening programs [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A080.</jats:p>
Authors
Ingraham, KL; Packenham, J; Harvey, D; Patierno, S; Barrett, NJ
MLA Citation
Ingraham, Kearston L., et al. “Abstract A080: Rates of Invitation, participation, and willingness to engage in medical and clinical research: Findings from attendees at two gender-specific community-based screening programs.” Cancer Epidemiology, Biomarkers &Amp; Prevention, vol. 29, no. 6_Supplement_1, American Association for Cancer Research (AACR), 2020, pp. A080–A080. Crossref, doi:10.1158/1538-7755.disp18-a080.
URI
https://scholars.duke.edu/individual/pub1467300
Source
crossref
Published In
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Volume
29
Published Date
Start Page
A080
End Page
A080
DOI
10.1158/1538-7755.disp18-a080

Abstract B050: Identification of differentially expressed and spliced genes between breast, colon, lung, and prostate cancer from African American and white patients

<jats:title>Abstract</jats:title> <jats:p>Racial/ethnic disparity in cancer refers to the disproportionate incidence of and/or mortality from various cancers among population groups. In addition to differences in social, lifestyle and structural determinants of health, there is accumulating evidence for a biologic contribution to racial/ethnic disparity in cancer. To understand further the biologic mechanisms underlying racial/ethnic disparity in cancer, the analysis of differential aggregate gene expression and mutation among cancer patients of different population groups is important. Our recently published work reported differential RNA splicing as a critical mechanism underlying prostate cancer aggressiveness and drug response in African American (AA) patients. Here, we use R to analyze the Genomic Data Commons for differential aggregate gene expression (2-fold mean change, p &amp;lt; 0.001, Wilcoxon rank sum test) and TCGASpliceSeq to analyze TCGA for differential RNA splicing (20% median change, percent spliced in) between breast (BRCA, 183 AA and 761 white), colon (COAD, 56 AA and 194 white), squamous and adenocarcinoma lung (LUSC and LUAD, 34 and 57 AA and 392 and 444 white, respectively), and prostate (PRAD, 49 AA and 307 white) cancer specimens from AA and white patients. Our analysis identified 698 differentially expressed genes (DEGs) and 114 alternative RNA splicing events (ARSs) in BRCA, 107 DEGs and 57 ARSs in COAD, 25 and 117 DEGs and 115 and 53 ARSs in LUSC and LUAD, respectively, and 25 DEGs and 71 ARSs in PRAD from AA and white patients. Notably, comparing the lists of DEGs or ARSs from each cancer type with each of the other cancer types yields a minority of overlapping DEGs or ARSs among cancer types, indicating that race-related DEGs and ARSs are largely specific to cancer type. Pathway analysis of DEGs and ARSs reveals that the majority of these genes function in pathways relevant to cancer development and progression, such as programmed cell death, DNA repair, signal transduction, gene expression and metabolism. These analyses increase understanding of molecular mechanisms underlying racial/ethnic disparity in cancer. Upon further study of the function of these variants, such DEGs and ARSs have the potential to become candidates for development of new precision medicine interventions.</jats:p> <jats:p>Citation Format: Muthana Al Abo, Daniel J. George, Jennifer A. Freedman, Steven R. Patierno. Identification of differentially expressed and spliced genes between breast, colon, lung, and prostate cancer from African American and white patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B050.</jats:p>
Authors
MLA Citation
Abo, Muthana Al, et al. “Abstract B050: Identification of differentially expressed and spliced genes between breast, colon, lung, and prostate cancer from African American and white patients.” Cancer Epidemiology, Biomarkers &Amp; Prevention, vol. 29, no. 6_Supplement_1, American Association for Cancer Research (AACR), 2020, pp. B050–B050. Crossref, doi:10.1158/1538-7755.disp18-b050.
URI
https://scholars.duke.edu/individual/pub1467301
Source
crossref
Published In
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Volume
29
Published Date
Start Page
B050
End Page
B050
DOI
10.1158/1538-7755.disp18-b050