Tino W. Sanchez

DFS70/LEDGFp75: An Enigmatic Autoantigen at the Interface between Autoimmunity, AIDS, and Cancer

Clinical and diagnostic laboratories often encounter patient sera containing antinuclear antibodies (ANAs) that produce a nuclear dense fine speckled immunofluorescence pattern on HEp-2 cells. These autoantibodies usually target the dense fine speckled protein of 70 kDa (DFS70), commonly known as lens epithelium-derived growth factor p75 (LEDGFp75). Anti-DFS70/LEDGFp75 autoantibodies have recently attracted much interest because of their relatively common occurrence in sera from patients with positive ANA tests with no clinical evidence of systemic autoimmune rheumatic disease (SARD). Their presence has been documented primarily in patients with diverse non-SARD inflammatory conditions and “apparently healthy” individuals. While there is circumstantial evidence that depending on the context these autoantibodies could play protective, pathogenic, or sensor roles, their significance remains elusive. DFS70/LEDGFp75 has emerged during the past decade as a stress transcription co-activator relevant to HIV integration, cancer, and inflammation. It is not clear, however, what makes this protein the target of such a common autoantibody response. We suggest that a better understanding of DFS70/LEDGFp75 biology is key to elucidating the significance of its associated autoantibodies. Here, we discuss briefly our current understanding of this enigmatic autoantigen and potential scenarios leading to its targeting by the immune system.

Using Serological Proteome Analysis to Identify Serum Anti-Nucleophosmin 1 Autoantibody as a Potential Biomarker in European-American and African-American Patients With Prostate Cancer.

The prostate‐specific antigen (PSA) testing has been widely implemented for the early detection and management of prostate cancer (PCa). However, the lack of specificity has led to overdiagnosis, resulting in many possibly unnecessary biopsies and overtreatment. Therefore, novel serological biomarkers with high sensitivity and specificity are of vital importance needed to complement PSA testing in the early diagnosis and effective management of PCa. This is particularly critical in the context of PCa health disparities, where early detection and management could help reduce the disproportionately high PCa mortality observed in African‐American men. Previous studies have demonstrated that sera from patients with PCa contain autoantibodies that react with tumor‐associated antigens (TAAs).

Targeting the stress oncoprotein LEDGF/p75 to sensitize chemoresistant prostate cancer cells to taxanes

Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy. We report here that the endogenous levels of LEDGF/p75 are upregulated in metastatic castration resistant prostate cancer (mCRPC) cells selected for resistance to the taxane drug docetaxel (DTX). These cells also showed resistance to the taxanes cabazitaxel (CBZ) and paclitaxel (PTX), but not to the classical inducer of apoptosis TRAIL. Silencing LEDGF/p75 effectively sensitized taxane-resistant PC3 and DU145 cells to DTX and CBZ, as evidenced by a significant decrease in their clonogenic potential. While TRAIL induced apoptotic blebbing, caspase-3 processing, and apoptotic LEDGF/p75 cleavage, which leads to its inactivation, in both taxane-resistant and -sensitive PC3 and DU145 cells, treatment with DTX and CBZ failed to robustly induce these signature apoptotic events. These observations suggested that taxanes induce both caspase-dependent and -independent cell death in mCRPC cells, and that maintaining the structural integrity of LEDGF/p75 is critical for its role in promoting taxane-resistance. Our results further establish LEDGF/p75 as a stress oncoprotein that plays an important role in taxane-resistance in mCRPC cells, possibly by antagonizing drug-induced caspase-independent cell death.

Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins

African American (AA) men suffer from a disproportionately high incidence and mortality of prostate cancer (PCa) compared with other racial/ethnic groups. Despite these disparities, African American men are underrepresented in clinical trials and in studies on PCa biology and biomarker discovery. We used immunoseroproteomics to profile antitumor autoantibody responses in AA and European American (EA) men with PCa, and explored differences in these responses. This minimally invasive approach detects autoantibodies to tumor-associated antigens that could serve as clinical biomarkers and immunotherapeutic agents. Sera from AA and EA men with PCa were probed by immunoblotting against PC3 cell proteins, with AA sera showing stronger immunoreactivity. Mass spectrometry analysis of immunoreactive protein spots revealed that several AA sera contained autoantibodies to a number of proteins associated with both the glycolysis and plasminogen pathways, particularly to alpha-enolase (ENO1). The proteomic data is deposited in ProteomeXchange with identifier PXD003968. Analysis of sera from 340 racially diverse men by enzyme-linked immunosorbent assays (ELISA) showed higher frequency of anti-ENO1 autoantibodies in PCa sera compared with control sera. We observed differences between AA-PCa and EA-PCa patients in their immunoreactivity against ENO1. Although EA-PCa sera reacted with higher frequency against purified ENO1 in ELISA and recognized by immunoblotting the endogenous cellular ENO1 across a panel of prostate cell lines, AA-PCa sera reacted weakly against this protein by ELISA but recognized it by immunoblotting preferentially in metastatic cell lines. These race-related differences in immunoreactivity to ENO1 could not be accounted by differential autoantibody recognition of phosphoepitopes within this antigen. Proteomic analysis revealed differences in the posttranslational modification profiles of ENO1 variants differentially recognized by AA-PCa and EA-PCa sera. These intriguing results suggest the possibility of race-related differences in the antitumor autoantibody response in PCa, and have implications for defining novel biological determinants of PCa health disparities.

Racial differences in the expression of inhibitors of apoptosis (IAP) proteins in extracellular vesicles (EV) from prostate cancer patients

African-American men with prostate cancer typically develop more aggressive tumors than men from other racial/ethnic groups, resulting in a disproportionately high mortality from this malignancy. This study evaluated differences in the expression of inhibitors of apoptosis proteins (IAPs), a known family of oncoproteins, in blood-derived exosomal vesicles (EV) between African-American and European-American men with prostate cancer. The ExoQuick™ method was used to isolate EV from both plasma and sera of African-American (n = 41) and European-American (n = 31) men with prostate cancer, as well as from controls with no cancer diagnosis (n = 10). EV preparations were quantified by acetylcholinesterase activity assays, and assessed for their IAP content by Western blotting and densitometric analysis. Circulating levels of the IAP Survivin were evaluated by ELISA. We detected a significant increase in the levels of circulating Survivin in prostate cancer patients compared to controls (P<0.01), with the highest levels in African-American patients (P<0.01). African-American patients with prostate cancer also contained significantly higher amounts of EVs in their plasma (P<0.01) and sera (P<0.05) than European-American patients. In addition, EVs from African-American patients with prostate cancer contained significantly higher amounts of the IAPs Survivin (P<0.05), XIAP (P<0.001), and cIAP-2 (P<0.01) than EVs from European-American patients. There was no significant correlation between expression of IAPs and clinicopathological parameters in the two patient groups. Increased expression of IAPs in EVs from African-American patients with prostate cancer may influence tumor aggressiveness and contribute to the mortality disparity observed in this patient population. EVs could serve as reservoirs of novel biomarkers and therapeutic targets that may have clinical utility in reducing prostate cancer health disparities.

Abstract 1130: Targeting the tumor-associated autoantigen alpha-enolase in prostate cancer

Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of cancer-related deaths in American men. African American (AA) men are more likely to be diagnosed with aggressive PCa at a younger age and twice as likely to die from the disease as European American (EA) men. In order to reduce PCa mortality and its associated racial disparities, there is a critical need to identify and target pathways responsible for PCa aggressiveness. An unexplored target is the plasminogen system, which is key to cancer cell migration and tissue invasion during metastasis. During inflammation, activation of the plasminogen pathway degrades extracellular fibrin networks; however, in the context of cancer, this activation promotes cancer tissue invasion and metastasis. Mounting evidence shows that the glycolytic enzyme alpha-enolase (ENO1) plays a vital role in both increased energy metabolism and plasminogen activation during cancer progression and metastasis. Using immunoseroproteomic profiling of anti-tumor autoantibody responses in AA and EA men with PCa, we identified several tumor-associated autoantigens with functions in glycolysis and plasminogen signaling, including ENO1, annexin A2, fructose bisphosphate aldolase, glucose-regulated protein 78, glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. In a cohort of PCa (N=157) and non-PCa sera (N=183), we found a significantly higher frequency of autoantibodies to ENO1 in patients with PCa (p Citation Format: Tino Wilson Sanchez, Guangyu Zhang, Jitian Li, Liping Dai, Saied Mirshahidi, Nathan R. Wall, Clayton Yates, Colwick Wilson, Susanne Montgomery, Jian-Ying Zhang, Carlos A. Casiano. Targeting the tumor-associated autoantigen alpha-enolase in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1130. doi:10.1158/1538-7445.AM2017-1130

Abstract B05: Differential autoimmune response to glycolysis and plasminogen antigens from aggressive prostate cancer cells in African American and European American men with prostate cancer

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related male deaths in the U.S. This cancer is more aggressive in African American (AA) men, who are twice as likely to die from the disease compared to other racial groups. Despite racial disparities in PCa mortality, immunoproteomic studies profiling sera from thousands of men for the presence of autoantibodies to tumor-associated antigens (TAA) have mostly used sera from European or Asian ancestry. These autoantibodies can serve as both cancer biomarkers and potential tools in anti-tumor immunotherapy. In this study we profiled sera of AA and European American (EA) men with (N=157) and without (N=183) PCa against protein lysates from aggressive PCa cell lines using one and two-dimensional Western blotting. Sera from AA-PCa patients showed stronger immunoreactivity to proteins in PC3 cell lysates compared to EA-PCa sera. Common bands of immunoreactivity were observed around 37, 40, 50, 55, 60, and 70 kD from the sera of multiple patients. Several AA-PCa sera showed common immunoreactivity against a 50 kD protein band (16 out of 24, 67%) which was identified by serological proteomic analysis (SERPA) as alpha-enolase (ENO1), an enzyme that participates in both the glycolysis and plasminogen pathways. ELISA using purified ENO1 was conducted on 360 sera and showed significantly elevated frequency in men with PCa compared to non-PCa controls. Interestingly, SERPA analysis of other strongly immunoreactive spots outside the 50 kD region recognized of the other highly reactive PCa sera revealed additional candidate TAAs involved in the glycolysis and plasminogen pathways. These included key glycolytic enzymes GAPDH, fructose bisphosphate aldolase, phosphoglycerate kinase and lactate dehydrogenase, and other members of the plasminogen system such as GRP78 and annexin A2. Autoantibodies to stress survival proteins HSP60 and STIP1 were also identified in multiple PCa sera. We then probed by immunoblotting representative sera recognizing some of these candidate TAAs against a panel of 12 PCa and non-PCa cell lines. Anti-STIP1 sera showed elevated immunoreactivity predominantly in docetaxel-resistant cell lines. In the anti-ENO1 positive sera, we observed a race-related differential immune response, with anti-ENO1 sera from AA-PCa men showing elevated immunoreactivity mostly in metastatic cell lines, and anti-ENO1 sera from EA-PCa men showing uniform immunoreactivity across the entire panel of prostate cell lines. Interestingly, while several anti-ENO1 positive sera from AA-PCa men had increased immunoreactivity to this protein in the metastatic PCa cell lines LNCaP, MDA-PC2b, PC3 and DU145, they lacked reactivity against ENO1 in the docetaxel-resistant PC3-DR and DU145-DR cells, or purified ENO1 used in the ELISA. Anti-ENO1 EA-PCa sera did not display this differential pattern of immunoreactivity. To better understand these differences in anti-ENO1 reactivity, we interrogated the pattern of ENO1 post-translational modifications (PTMs) from PC3, PC3-DR and purified ENO1. Several different acetylated, methylated, phosphorylated, citrullinated, and glycosylated ENO1 PTMs were identified in the PC3 cells that were not present in the PC3-DR cells nor purified ENO1 which might explain the differential reactivity of AA-PCa sera against these three sources of ENO1. Taken together, these data suggest the anti-ENO1 autoantibodies from AA-PCa men may target a modified form of ENO1 that is different from that recognized by EA-PCa men. These discrepancies point to racial differences in immune response to TAAs in prostate tumors, and may have implications for identifying immunobiological factors contributing to PCa health disparities. Citation Format: Tino W. Sanchez, Guangyu Zhang, Jitian Li, Liping Dai, Rowaid Kellow, Saied Mirshahidi, Nathan R. Wall, Clayton Yates, Colwick Wilson, Susanne Montgomery, Jian-Ying Zhang, Carlos Casiano. Differential autoimmune response to glycolysis and plasminogen antigens from aggressive prostate cancer cells in African American and European American men with prostate cancer. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B05.

Abstract 3895: Immunoproteomic profiling in African American men with prostate cancer: Evidence for an autoimmune response to glycolytic enzymes

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related male deaths in the U.S. This cancer is more aggressive in African American (AA) men, who are twice as likely to die from the disease when compared to other racial groups. Despite these racial disparities in PCa mortality, studies on PCa biology and biomarker discovery include mostly patients from European American (EA) backgrounds. There is a critical need to find minimally invasive PCa biomarkers that could aid in diagnosis and prognosis, especially in high risk populations like AA men. Immunoproteomics offers a minimally invasive approach to detect early malignant processes that trigger production of autoantibodies to tumor-associated antigens (TAA). We used serum samples from AA (n = 59) and EA (n = 50) men with PCa to probe one- and two-dimensional Western blots of protein lysates from aggressive PCa cell lines. AA PCa patient sera showed stronger immunoreactivity to proteins in PC3 cell lysates compared to the EA sera, with a 50 kD protein band frequently targeted by autoantibodies in several AA PCa sera. Serological proteomic analysis with mass spectrometry showed that these AA PCa autoantibodies recognized alpha-enolase (ENO1), a protein important in tumor formation, expansion, and glucose metabolism. In addition, several other glycolytic enzymes important for tumor proliferation were also identified as candidate prostate TAA, including GAPDH, bisphosphate aldolase, phosphoglycerate kinase, and lactate dehydrogenase. The ENO1 autoantibody frequency, measured by ELISA in sera from 400 racially diverse men with and without PCa, was four-fold higher in PCa compared to non-PCa patients. Interestingly, although sera from AA men with PCa had stronger WB reactivity to ENO1 present in PC3 lysates compared to EA men, and the ENO1 autoantibodies were initially discovered in eight AA PCa sera but only in two EA sera, the anti-ENO1 autoantibody frequency measured by ELISA, which used yeast-purified recombinant human ENO1 as a substrate, was higher in the EA PCa cohort. In addition, several anti-ENO1 positive sera from AA men with PCa showed increased immunoreactivity to this protein in the PCa cell lines LNCaP, MDA-PC2b, PC3, and DU145, but not against the purified ENO1 used in ELISA. The opposite was true in the EA PCa cohort, where strong reactivity against the purified ENO1 did not correlate with an equally strong immunoreactivity against the cellular ENO1. The EA PCa sera did not recognize the pattern of ENO1 expression observed with the AA sera in the same panel of prostate cell lines. These differences of immunoreactivity between AA and EA sera against PC3-ENO1 vs recombinant human ENO1 suggest that select AA sera may predominantly recognize ENO1 epitopes not displayed in the purified protein. These discrepancies point to racial differences in the immune response to prostate tumors. Citation Format: Tino Wilson Sanchez, Jian-Ying Zhang, Liping Dai, Susanne Montgomery, Colwick Wilson, Guangyu Zhang, Saied Mirshahidi, Nathan Wall, Carlos A. Casiano. Immunoproteomic profiling in African American men with prostate cancer: Evidence for an autoimmune response to glycolytic enzymes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3895.

Abstract B05: Immunoproteomic profiling in African American men with prostate cancer: Evidence for an autoimmune response to glycolytic enzymes

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related male deaths in the U.S. This cancer is more aggressive in African American (AA) men, who are twice as likely to die from the disease when compared to other racial groups. Despite these racial disparities in PCa mortality, studies on PCa biology and biomarker discovery include mostly patients from European American (EA) backgrounds. There is a critical need to find minimally invasive PCa biomarkers that could aid in diagnosis and prognosis, especially in high risk populations like AA men. Immunoseroproteomics offers a minimally invasive approach to detect early malignant processes that trigger production of autoantibodies to tumor-associated antigens (TAA). These antibodies serve as “sensors” of tumorigenic events and can be assessed as potential biomarkers relevant to tumor biology. In this study we used this approach to interrogate anti-TAA autoantibody signatures in AA and EA men with PCa and explored racial differences in tumor immunobiology that could underlie PCa mortality disparities. We used serum samples from AA (n=59) and EA (n=50) men with PCa to probe one- and two-dimensional Western blots (WB) of protein lysates from aggressive PCa cell lines. AA PCa patient sera showed stronger immunoreactivity to proteins in PC3 cell lysates compared to the EA sera, with a 50 kD protein band frequently targeted by autoantibodies in several AA PCa sera. Serological proteomic analysis (SERPA) with mass spectrometry showed that these AA PCa autoantibodies recognized alpha-enolase (ENO1), known to be important in tumor formation, expansion, and glucose metabolism. In addition, several other glycolytic enzymes important for tumor proliferation were also identified as candidate prostate TAA, including GAPDH, phosphoglycerate kinase, and lactate dehydrogenase. These have been validated in other studies as overexpressed in PCa. The ENO1 autoantibody frequency, measured by ELISA in sera from 400 racially diverse men with and without PCa, was four-fold higher in PCa compared to non-PCa patients. Interestingly, although sera from AA men with PCa had stronger WB reactivity to ENO1 present in PC3 lysates compared to EA men, and the ENO1 autoantibodies were initially discovered in eight AA PCa sera but only in two EA sera, the anti-ENO1 autoantibody frequency measured by ELISA, which used E. coli-purified recombinant human ENO1 as a substrate, was higher in the EA PCa cohort. In addition, several anti-ENO1 positive sera from AA men with PCa showed increased immunoreactivity to this protein in the PCa cell lines LNCaP, MDA-PC2b, PC3, and DU145, but not against the purified ENO1 used in ELISA. The opposite was true in the EA PCa cohort, where strong reactivity against the purified ENO1 did not correlate with an equally strong immunoreactivity against the cellular ENO1. The EA PCa sera did not recognize the pattern of ENO1 expression observed with the AA sera in the same panel of prostate cell lines. These differences of immunoreactivity between AA and EA sera against PC3-ENO1 vs bacterially purified human ENO1 suggest that select AA sera may predominantly recognize ENO1 epitopes not displayed in the purified protein. A recent study found higher frequency of autoantibodies to phosphorylated ENO1 in pancreatic cancer sera compared to normal patient sera. Our own proteomic comparison of PC3-ENO1 and recombinant ENO1 yielded differences in phosphorylated, acetylated, and methylated amino acids. Taken together, these data suggest the anti-ENO1 autoantibodies from AA men with PCa target a modified form of ENO1 that may not be strongly recognized by EA men with PCa. These discrepancies point to racial differences in the immune response to prostate tumors. Citation Format: Tino Wilson Sanchez, Jitian Li, Liping Dai, Saied Mirshahidi, Guangyu Zhang, Nathan Wall, Colwick Wilson, Susanne Montgomery, Jianying Zhang, Carlos Casiano. Immunoproteomic profiling in African American men with prostate cancer: Evidence for an autoimmune response to glycolytic enzymes. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B05.

Abstract B06: Repositioning HIV-based small molecule inhibitors of the stress oncoprotein LEDGF/p75 to overcome prostate cancer resistance to taxane chemotherapy

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths in men. In addition, African American (AA) men have a higher incidence of PCa with more aggressive tumors and increased mortality compared to other ethnic groups. The rise in the U.S. aging male population and the health disparities associated with this cancer type, are expected to make PCa a formidable public health and fiscal challenge in the next few decades. PCa mortality is driven by the ability of advanced prostate tumors to metastasize to vital organs and develop resistance against established anti-androgen therapies and chemotherapeutic drugs. Despite recent developments in the treatment of advanced PCa, the high mortality and the racial disparities associated with this disease still persist. For this reason, there is still an urgent medical need for innovative therapeutic approaches to reduce the burden of PCa mortality and its associated disparities. Our laboratory is at the forefront of research on the contribution of the lens epithelium-derived growth factor of 75 kD (LEDGF/p75) to PCa cancer aggressiveness. This protein is a stress response transcription coactivator that is overexpressed in PCa cells and clinical tumors, transcriptionally upregulates stress survival proteins in cancer cells, and promotes resistance to Docetaxel (DTX), the first line chemotherapeutic drug used to treat advanced PCa. Interestingly, LEDGF/p75 also plays a critical role in facilitating the integration of human immunodeficiency virus 1 (HIV-1) into active host chromatin by interacting with the HIV-integrase (HIV-IN). This biological function has made LEDGF/p75 an attractive druggable target, and for this purpose a series of novel and potent small molecule inhibitors (SMI) have been designed and studied to disrupt the interaction between HIV-IN and the C-terminal region of LEDGF/p75, which we previously implicated in its pro-survival activity. We hypothesize that repositioning these SMI for PCa treatment in combination with DTX is an innovative approach to re-sensitize DTX resistant PCa cells to chemotherapy. We observed that PC3 and DU145 cells selected for DTX resistance expressed high levels of LEDGF/p75, and were also selectively resistant to the taxanes Cabazitaxel (CTX) and Paclitaxel (PTX), but not to the classical apoptosis inducer TRAIL. Immunoblotting analysis indicated that LEDGF/p75 is cleaved and inactivated by caspases during TRAIL-induced cell death, whereas the protein remained intact in taxane treated cells. RNA interference-mediated knockdown of LEDGF/p75 in DTX-resistant cell lines sensitized them to taxane therapy. This provided proof of principle that functional inactivation of LEDGF/p75 could restore chemosensitivity. We then screened a panel of over 100 HIV-based candidate LEDGF/p75 SMI for their cytotoxicity against DTX-resistant and -sensitive PCa cells, in the presence and absence of DTX. These experiments yielded a number of inhibitors that re-sensitized the resistant cells to taxane treatment. We are currently expanding these studies to a panel of racially diverse PCa cell lines to determine the efficacy of this approach in multiple PCa cell types. Taken together, our results suggest that LEDGF/p75 is a druggable target that could potentially be functionally inactivated by repositioned HIV-based inhibitors in combination with established chemotherapeutic regimens to circumvent PCa chemoresistance and reduce the mortality disparities associated with the aggressive form of this disease. Citation Format: Leslimar Rios-Colon, Tino Wilson Sanchez, Catherine C. Elix, Ivana Alicea, Anamika Basu, Christina Du Ross, Nouri Neamati, Carlos A. Casiano. Repositioning HIV-based small molecule inhibitors of the stress oncoprotein LEDGF/p75 to overcome prostate cancer resistance to taxane chemotherapy. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B06.