e16554 Background: Annually, there are over 400,000 new renal cell carcinoma (RCC) cases and more than 170,000 deaths worldwide. RCC is one of the top ten more prevalent malignancies in the United States, with 76,000 new cases each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. Studies demonstrate histologic differences and outcome disparities among Hispanic and Latino patients diagnosed with RCC. Research to date describes earlier and more advanced diseases at diagnosis, higher rates of obesity at presentation, and higher mortality among these cohorts. However, there is limited data on clinical, pathological, molecular, and treatment outcomes in this patient population. This study aims to characterize clinical features and treatment outcomes in this patient population in South Florida. Methods: We conducted a retrospective cohort study to describe the characteristics and rates of recurrence of RCC among patients treated at Sylvester Comprehensive Cancer Center in Miami (which serves four counties in South Florida) between June 2010 to June 2022. An IRB-approved advanced RCC database was developed on RedCap, where clinical, laboratory, pathological, treatment, and response information were captured. Ethnicity was determined as Hispanic/Latino (HL) or non-Hispanic/Latino (NHL). Clinical groups were classified based on the last encounter as local RCC after nephrectomy, recurrent metastatic RCC after nephrectomy, and metastatic RCC at diagnosis/de novo. Results: We analyzed a total of 2048 patients aged 18 and older diagnosed with RCC, from which 1008 patients (47.70%) were identified as NHL and 963 (47.92%) as HL. RCC was in over a 2:1 ratio of men to women in both HLs and NHLs. A subtotal of 435 patients (22.87%) had metastatic RCC at diagnosis/de novo, from which 245 (55.59%) were NHL, and 175 (40.32%) were HL. A subtotal of 1613 patients (78.76%) were diagnosed with local RCC and underwent nephrectomy, from which 763 (45.46%) were identified as NHL and 788 (50.15%) as HL. From the NHL group that underwent nephrectomy, 222 patients (28.21%) had recurrent disease, and 541 patients (71.79%) did not. From the HL group, 175 patients (21.69%) had recurrent disease, and 613 (78.31%) did not. Overall, 408 patients had metastasis after nephrectomy, of which 175 (44.31%) were HL, and 203 (52.24%) were NHL. Conclusions: In this cohort of patients with RCC, over 40% of patients diagnosed with metastasis were HL. NHL appeared to have more disease recurrence after nephrectomy and higher rates of metastatic disease at diagnosis compared to Hispanics. Further histopathological differences, clinical outcomes, genomic characterization, and rates of clinical trial participation between the NHL and HL cohorts will be presented at the meeting, along with comparisons between US and foreign-born HLs.

Background: While advances in immune and targeted therapies improve outcomes in selected cancers, only a minority of colorectal cancer (CRC) patients benefit from them. Oncolytic viruses (OVs) represent novel cancer biotherapies, and among them, the oncolytic measles virus (MV) has demonstrated safety and antitumor activity in early clinical studies. MV alone does is not associated with cancer cures. Triptolide, a diterpenoid epoxide extracted from the thunder god vine (Tripterygium wilfordii), has been reported to have potent antitumor effects via multiple mechanisms, including anti-proliferative, pro-apoptotic, antiangiogenic, and induction of ER stress. The effects of triptolide on viral colon cancer oncolysis have not been previously investigated. Objectives: To characterize the in vitro and in vivo mechanisms of novel stromal retargeted oncolytic MVs and improve efficacy by combining MVs with triptolide. Methods: The in vitro effects of triptolide alone, MV-GFP (Edmonston strain of Measles virus expressing eGFP, for human cancer cells), MV-m-uPA (MV retargeted against the murine uPA receptor, for murine cancer cells), or virus-triptolide combinations on tumor cell cytotoxicity were assessed by cell count (Vi cell counter) or xCelligence assays, on HT-29, HCT116, SW620, CT26, and MC38 cells. Molecular and mechanistic characterization of Triptolide’s effects alone and combination with MV in HT29 cells will be analyzed by the (Reverse Phase Protein Array (RPPA) and validated by western blot analysis (experiment undergoing). In vivo effects (tumor progression and survival) of minnelide (M) (water-soluble version of Triptolide) alone and in combination with Measles Virus were assessed in Balb/C mice bearing CT26. Results: While MV and T had dose-dependent cytotoxic activity as single agents, significant augmentation of MV oncolysis was induced by co-treatment with triptolide. In vivo experiments showed similar effects observed in vitro, with potent antitumor activity of triptolide and enhanced in vivo antitumor activity when minnelide was combined with MV vectors. Conclusions: our results strongly suggest that triptolide or minnelide enhances measles virus oncolysis in vitro and in vivo models of colorectal cancer. In vitro and in vivo mechanistic studies are underway to characterize the molecular mechanisms by which triptolide enhances MV oncolysis and will be presented at the meeting. Citation Format: Valery A. Chavez, Floritza Bustamante, Abner Murray, Ashok Saluja, Jaime Merchan. A novel virus-drug combination to enhance oncolysis in colorectal cancer (crc) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 96.

Background: The worldwide incidence of Renal Cell Carcinoma (RCC) is increasing. Although new therapies have improved outcomes in advanced RCC, most patients eventually fail treatment and succumb to this devastating disease. Systemic therapy strategies have focused on TKI and immunotherapy, alone or in combination. Triptolide, a diterpenoid epoxide extracted from Tripterygium wilfordii Hook f (TWHf), has potent antitumor activity in multiple cancer models. Few studies have focused on the potential of triptolide as a novel therapeutic option in RCC. Objective: the objectives of this study are to characterize the in vitro and in vivo effects of Triptolide (T) and its water-soluble form, Minnelide (M), in models of renal cell carcinoma. Methods: The in vitro effects of triptolide (T) on human and murine RCC (786-0, A498, Caki-1, ACHN, and RENCA) cell proliferation was assessed using cell count and xCelligence assays at 24, 48, 72 and 96h. Molecular and mechanistic characterization of triptolide’s effects in 786-0 cells were analyzed by the (Reverse Phase Protein Array) and validated by western blot analysis. The in vivo effects (tumor progression and survival) of M were assessed in nude mice bearing 786-0 tumors (8x106 cells per mouse). M was administered to tumor-bearing mice at two different doses (0.21mg/kg and 0.42mg/kg daily), intraperitoneally, for 21 days. Correlative studies to explain the in vivo effect of M and the correlation with the molecular changes in vitro seen are being performed and will be shown in the poster. Results: T significantly inhibited, in a dose-response manner, cell proliferation in all human and murine renal cancer cell lines, with IC50 ranging between 12.5 and 25 nM). T was associated with significant negative modulation of proliferation, cell cycle, survival, increased apoptosis, and ER stress pathways in 786-0 cells, as demonstrated by RPPA analysis and validated by western Blot of selected pathway proteins, such as apoptosis (PARP cleavage and Caspase 3 activation), ER stress induction (pEIF2a, CHOP), and down-regulation of survival and proliferation pathways (pAKT). In vivo, M was associated with significant antitumor effects in 786-0 xenografts, with complete responses in the majority of mice while on treatment. These effects were associated with significant prolongation in overall survival in M treated vs. control mice. No significant toxicity or treatment-related deaths were observed. Conclusion: Our results have shown for the first time the potent in vitro and in vivo antitumor effects of T in RCC and the molecular changes associated with these effects. The profound antitumor effects in the aggressive 786-0 RCC xenograft model are highly encouraging and warrant further preclinical studies and potential clinical trials of M this devastating disease. Correlative tumor studies to understand the mechanisms of M in vivo antitumor effects are underway and will be presented at the meeting. Citation Format: Valery A. Chavez, Floritza Bustamante, Abner Murray, Ashok Saluja, Jaime Merchan. In vitro, in vivo and molecular effects of triptolide and minnelide in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 95.

e16555 Background: Annually, there are over 400,000 new renal cell carcinoma (RCC) cases and more than 170,000 deaths worldwide. In the US, 80,000 new cases of RCC are diagnosed each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. RCC seems to have a greater incidence among Hispanics, with a nearly three-fold increase. The epidemiology of RCC in the Caucasian population has been previously studied. However, there is a knowledge gap on disparities in RCC on minority populations. Studying the epidemiology of RCC in Hispanics is integral to our community, where Hispanics make up 70%. Methods: We conducted a retrospective cohort study using the Florida Statewide Cancer Registry to describe the characteristics and rates of metastatic RCC (mRCC) among patients in the State between 1981 and April 2019. We identified ethnicity as Hispanic/Latino (HL) or non-Hispanic/Latino (NHL). Clinical presentation was categorized as mRCC at diagnosis/de novo based on SEER and TNM classification. Results: We analyzed 81,178 patients age 18 and older with an ICD-10 code C649 diagnosis of malignant neoplasm of an unspecified kidney. 69,359 patients (85%) were diagnosed with RCC based on ICD-O classification, and 10,959 (13%) had metastatic disease at the time of diagnosis. Of these patients with metastatic disease, 9,691 (87.12%) were identified as NHL and 1,170 (12.30%) as HL. At the time of diagnosis, more HLs were enrolled in Medicaid (11.99% vs. 4.03%) and were uninsured (9.36% vs. 4.28%) compared to NHLs. Amongst HLs with the country of birth data, 650 (87%) were foreign-born and 97 (13%) were US-born. The largest group of foreign-born HLs was from Cuba, with 337 patients (45.18%). While for both groups the highest number of patients were diagnosed in the seventh decade of life (USA 29.66% vs. foreign 27.23%), USA-born HLs were diagnosed more over the preceding two decades (age 39-58) than foreign-born HLs (45.82% vs. 33.51%). Conversely, foreign-born HLs were diagnosed later than US-born HLs (35.29% vs. 18.34%). Both groups kept the same top two histological diagnoses (RCC and ccRCC) as the general cohort; however, US-born HLs were diagnosed with spindle cell carcinoma almost twice as much as foreign-born HLs (10.27% vs. 5.36%). Lastly, 85% of US-born HLs received treatment after diagnosis of mRCC compared to 78.9% of foreign-born HLs; however, at the last update, 47.17% and 32.95% were alive, respectively. Conclusions: In this cohort of patients with mRCC, 1 of 10 patients diagnosed with mRCC was HL. While characteristics were similar between groups, HLs had differences regarding access to care. Even amongst HLs, the country of origin affected the age of diagnosis, treatments, and outcomes. Further histopathologic and clinical characteristics will be presented at the meeting, along with treatment choices, outcomes, and clinical trial participation in the NHL and HL cohorts.