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The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.

Background: The percentage of positive cores (PPC) is increasingly recognized as a prognostic factor in prostate cancer. However, the usefulness of PPC for patients undergoing androgen deprivation therapy (ADT) and high-risk group has not been adequately studied. Methods: A retrospective analysis was conducted of 255 patients who underwent prostate biopsy (all-case group). We examined the efficacy of PPC as a prognostic biomarker. Results: Eighty-nine patients were treated with ADT alone (ADT group), and 107 patients were classified as high-risk (high-risk group). The median duration of follow-up was 112.4 months, 85.3 months, and 110.0 months for the all-case group, ADT group, and high-risk group, respectively. Patients with PPC >60% had significantly shorter prostate cancer-specific survival (CSS) and castration-resistant prostate cancer-free survival (CFS) in the all-case group and ADT group. In high-risk group, patients with PPC >60% had shorter CFS but no difference in CSS. Multivariate analysis showed that significant independent predictors of prostate CSS were the presence of metastasis at diagnosis and PPC >60% in the all-case group and ADT group. Conclusions: This study demonstrates that PPC may be a prognostic factor in ADT treatment and high-risk patients.

Background/Aim: The current standard of care for first-line treatment of locally advanced or metastatic urothelial carcinoma (UC) is platinum-based combination chemotherapy. Recently, immune checkpoint inhibitors have been reported to be effective for UC. Knowing whether immunotherapy or chemotherapy is suitable as first-line treatment is beneficial for patients. A retrospective study was conducted on the clinical outcomes of Japanese patients who received three or more courses of first-line chemotherapy for metastatic UC to assess the outcome of conventional treatments in real clinical situation. Patients and Methods: Patients who received first-line chemotherapy between August 2009 and December 2019 were included. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: The median PFS and OS were 7.1 and 27.1 months, respectively, for patients with no disease progression at the end of three courses. Of 28 patients, 25 (89.3%) received second-line drug therapy and 10 (35.7%) received focal therapy for disease control. Patients with focal therapy had significantly longer OS than those without focal therapy (p=0.019, log-rank test). Conclusion: OS of metastatic UC at our Institution is relatively long, suggesting that aggressive second-line drug therapy and focal therapy may have contributed to such result.

Background/aim Cabazitaxel is recommended as first-line treatment after docetaxel for metastatic castration-resistant prostate cancer. However, the efficacy, adverse events and prognostic factors associated with cabazitaxel are unclear. Patients and methods This single-centre retrospective study including 30 patients with CRPC treated with cabazitaxel between 2014 and 2020 investigated efficacy, outcomes and prognostic factors. Results Fourteen patients had visceral metastases. The median cabazitaxel dose was 20 mg/m2 The prostate-specific antigen response rate, time to prostate-specific antigen response, and overall survival were 13.3%, 3.48 months, and 7.92 months, respectively. The rates of grade 3 or more neutropenia and febrile neutropenia were 20% and 6.7%, respectively. By multivariate analysis, sarcopenia and visceral metastasis at the time of cabazitaxel initiation were independent and significant factors conferring a poor prognosis. Conclusion The early introduction of cabazitaxel, prior to the development of sarcopenia and visceral metastasis, might contribute to improved prognosis in CRPC.

A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of ≥ 7 and 273 had a GS of 24, PSA density ≥ 0.24 ng ml−2, positive findings on digital rectal examination, and transrectal with 90.0% sensitivity and 67.4% specificity. In this study, we found that raising the PSA cutoff to 12 ng ml−1 for CSPC in elderly individuals can significantly reduce unnecessary prostate biopsies. Furthermore, CSPC could be efficiently discovered by combining the four supplementary markers in patients with a PSA level of 4–12 ng ml−1. By performing this screening for elderly men over 75 years of age, unnecessary biopsies may be reduced and CSPC may be detected efficiently.

Background/aim This study aimed to assess the efficacy and toxicity of second-line chemotherapy, especially combination chemotherapy, for advanced or metastatic urothelial cancer. Patients and methods This retrospective analysis included patients who received second-line chemotherapy after disease progression during first-line chemotherapy between January 2009 to May 2018. Progression-free survival (PFS), overall survival (OS) and toxicity associated with second-line chemotherapy were assessed. Results In total 25 patients received second-line chemotherapy; 21 patients had combination chemotherapy and 4 had single-agent chemotherapy. Median PFS and OS were 3.6 months (range=0.2-23.5) and 11.9 months (range=0.5-29.0), respectively. Twenty patients (80%) exhibited grade 3 or more severe toxicities. Conclusion PFS and OS benefits of second-line combination chemotherapy corresponded to those of the phase 3 study of pembrolizumab, but adverse events were more severe. Pembrolizumab is potentially a better second-line treatment than combination chemotherapy.

Background/aim To evaluate the chronological changes in health-related quality of life and treatment satisfaction after robot-assisted radical prostatectomy (RARP). Patients and methods A total of 196 patients were included, and treatment satisfaction was evaluated using the Expanded Prostate Cancer Index Composite (EPIC) score before and at 1, 3, 6, and 12 months after RARP. Results At 12 months after RARP, 64.8% of patients were satisfied. On the contrary, 4.6% of patients were dissatisfied at 12 months after RARP. In a multivariate analysis, only urinary bother of EPIC was significantly associated with satisfaction at 12 months after RARP (p=0.025, odds ratio=1.029). Conclusion Treatment satisfaction with RARP was generally acceptable from 1 to 12 months after surgery and did not change over time. Urinary bother was associated with satisfaction at 12 months after RARP. Compared with the objective 24-hour pad test, questionnaires answered subjectively were more associated with satisfaction.

Background/aim Vintage hormone therapy for non-metastatic castration-resistant prostate cancer (nmCRPC) is not recommended under the current guidelines, but is widely practiced in Japan. This study assessed effectiveness of vintage hormone therapy as alternative androgen deprivation therapy (AADT) for treatment of nmCRPC. Patients and methods In this retrospective study we examined patients with nmCRPC that received vintage hormone therapy as AADT between 1999 and 2018. Results Of 53 patients with nmCRPC, 25 patients (47.2%) had stage 1 nodal disease (N1) at diagnosis of nmCRPC. Prostate specific antigen (PSA) reduction rate≥30% was observed in 32 patients (72.7%). The median PSA nadir was 0.7, and the duration of the response was 14.3 months. The median metastasis-free survival (MFS) for the entire patient population was 62.2 months, and the median overall survival (OS) was not reached. In the multivariate analysis, the duration of response in AADT>18 months was a predictor of prolonged OS. Conclusion There is a certain number of nmCRPC patients who respond well to vintage hormone therapy as AADT. Further studies are expected to differentiate such cases.

Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P P

Despite improvements in systemic therapy options for renal cancer, it remains one of the most drug-resistant malignancies. Interestingly, reports have shown that kahweol and cafestol, natural diterpenes extracted from coffee beans, exhibit anti-cancer activity. However, the multiple potential pharmacological actions of both have yet to be fully understood. This study therefore investigated the effects of kahweol acetate and cafestol on human renal cancer ACHN and Caki-1 cells. Accordingly, the combination of kahweol acetate and cafestol administration synergistically inhibited cell proliferation and migration by inducing apoptosis and inhibiting epithelial–mesenchymal transition. Mechanistic dissection revealed that kahweol acetate and cafestol inhibited Akt and ERK phosphorylation. Moreover, kahweol acetate and cafestol downregulated the expression of not only C–C chemokine receptors 2, 5, and 6 but also programmed death-ligand 1, indicating their effects on the tumor microenvironment. Thus, kahweol acetate and cafestol may be novel therapeutic candidates for renal cancer considering that they exert multiple pharmacological effects.

Background/aim Hypertension is a risk factor for occurrence of renal cell carcinoma; however, it remains unclear whether hypertension affects development and prognosis of renal cell carcinoma. This study evaluated the impact of hypertension on the progression of renal cell carcinoma. Patients and methods Renal cell carcinoma patients who were treated from October 2007 to December 2018 at our Institution were retrospectively analyzed. Results Of 462 patients, the number of patients with and without hypertension was 234 (including 227 treated with anti-hypertensive agents) and 228, respectively. The tumor size was significantly smaller in the hypertension group than in the non-hypertension group (median 32 and 45 mm, respectively, p=0.010). The 5-year cancer-specific and metastasis-free survival in the hypertension group were significantly better than those in the non-hypertension group (93.6% and 80.4%, and 84.6% and 73.0%, respectively, p=0.021 and p=0.017). Propensity score matching revealed significantly better metastatic-free survival in the hypertension group than the non-hypertension group (p=0.022). Conclusion Renal cell carcinoma patients with hypertension show better prognosis with low metastasis possibility.

We appreciate Zins and Abraham [1] commenting on our paper studying the role of the CCL20-CCR6 axis on renal cell carcinoma (RCC) cells [2]. As they pointed out, our study has certain limitations. Although M1- and M2-types cannot be separated clearly and a consecutive change of character might exist between them, it has been reported that plural specific markers express on M1- and M2-types. Unfortunately, a definite difference between M1 and M2 macrophages was not confirmed in our study. For more differentiation, multiple stimulations, such as suggested in the comments of Zins and Abraham, might be needed. Hence, we needed to expediently use “M1-like” and “M2-like” to mention specific status of these macrophage-like cells. Meanwhile, CCL20 expression levels of M2-like-THP-1 cells co-cultured with RCC cells were dramatically increased compared with parental THP-1 cells, indicating that certain stimulations within the tumor microenvironment rather than theoretical stimulations make macrophages differentiated; however, further studies are needed to clarify this mechanism using a more appropriate co-culture system mimicking the tumor microenvironment. Immunohistochemistry of CCL20 and M2 markers will help to better understand the role of tissue infiltrating macrophages, even tissue CD68 staining intensity itself was reported to correlate with prognosis of RCC patients [3]. [...]

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial&ndash, mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial&ndash, mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial&ndash, mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial&ndash, mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.

Once castration-resistant prostate cancer (CRPC) become resistant for cabazitaxel treatment, the patients are obliged to best supportive care. Therefore, the elucidation of the mechanism of the cabazitaxel-resistance and the conquest are important themes to improve the prognosis of the patients. Then we tried to establish cabazitaxel-resistant CRPC cell lines and characterized them. We established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR from PC-3-TxR and DU145-TxR cell lines previously we established. PC-3-TxR/CxR and DU145-TxR/CxR cells became resistant for cabazitaxel by 11.8-fold and 4.4-fold, respectively. The TxR/CxR cells showed cabazitaxel-resistant using SCID mice in vivo. Although expression of multi-drug resistance gene 1 (MDR1) was up-regulated in DU145-TxR compared with DU145 cells, it was not up-regulated in DU145-TxR/CxR cells any more. In contrast, expression of MDR1 gene was up-regulated in PC-3-TxR compared with PC-3 cells and it was further up-regulated in PC-3-TxR/CxR compared with PC-3-TxR cells. Comparison of cDNA microarray between PC-3-TxR and PC-3-TxR/CxR cells or between DU145-TxR and DU145-TxR/CxR cells revealed that many genes were up-regulated or down-regulated. Finally, knockdown of MDR1 recovered the sensitivity to cabazitaxel not only in PC-3-TxR/CxR cells but also DU145-TxR/CxR cells. Together, regulation of MDR1 gene is important for conquest of the cabazitaxel-resistance.

Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling.

Introduction Renal transplantation often causes polyuria, and a Foley catheter is typically placed after transplantation. A urethral stricture often makes it difficult to insert a normal diameter urethral catheter. Case presentation We report on the case of a 16-year-old adolescent male with a history of hypospadias surgery who underwent a cystostomy during renal transplantation. A cystostomy was placed during transplantation because of stricture of the pendulous urethra. Urine leakage into the retroperitoneum occurred after cystostomy catheter removal. An 8-Fr urethral catheter was placed, and urine was aspirated to prevent drainage failure. Voiding cystourethrography performed after 2 weeks showed that there was no leakage. After that, the patient had no trouble with urination. Conclusion A cystostomy may be one strategy for renal transplantation patients with a urethral stricture. Urine leak can occur because of the delay in wound healing caused by immunosuppressive therapy. Therefore, cystostomy management strategies should be considered carefully.

α-Trifluoromethyl chalcones were prepared and evaluated for their antiproliferative activities against androgen-independent prostate cancer cell lines as well as five additional types of human tumor cell lines. The most potent chalcone 5 showed superior antitumor activity in vivo with both oral and intraperitoneal administration at 3 mg/kg. Cell-based mechanism of action studies demonstrated that 5 induced cell accumulation at sub-G1 and G2/M phases without interfering with microtubule polymerization. Furthermore, several cancer cell growth-related proteins were identified by using chalcone 5 as a bait for the affinity purification of binding proteins.

Urachal cancer often presents at an advanced stage with poor prognosis due to the lack of an effective systematic therapeutic strategy. We experienced a case of metastatic urachal cancer treated effectively by combination chemotherapy and radiotherapy. A 55-year-old female presented to our department with right lower abdominal pain. A transurethral biopsy of an urachal tumor suggested urachal adenocarcinoma. The patient underwent chemotherapy with gemcitabine and cisplatin for metastatic urachal cancer. As tumor markers declined and the radiological findings indicated stability of disease, external beam radiotherapy was then administered to the primary site. Chemotherapy was then administered again in response to tumor markers gradually increasing and the progression of multiple peritoneal metastases. However, the patient did not complete chemotherapy due to hematological toxicity. The patient succumbed to primary disease 23 months after initial diagnosis. Previous studies have reported that the median time from the diagnosis of metastatic urachal cancer to mortality is just over 1 year. By contrast, in the present case the patient survived up to 2 years with combination chemotherapy and radiotherapy, a rare incidence worthy of reporting.

Background The present study was conducted to investigate whether baseline serum carbohydrate antigen (CA) 19-9 predicts prognosis or treatment effect in patients with advanced urothelial carcinoma (UC). Materials and methods We retrospectively analyzed data of patients diagnosed with locally advanced or metastatic or recurrent UC between April 2008 and November 2014. CA19-9 was determined using enzyme-linked immunosorbent assay (ELISA) and the relationship between CA19-9 and prognosis were analyzed. Results Of 40 patients, seven with CA19-9 ≤2 U/ml who were suspected of having Lewis A-negative blood type and two patients with advanced metastatic liver disease were excluded. UC-specific survival in metastatic disease significantly correlated with prognosis (p=0.018). Overall survival in patients with high serum CA19-9 demonstrated a significantly better prognosis than in those with low concentrations (log-rank test, p=0.032). Conclusion High baseline serum CA19-9 may predict a good prognosis in patients with advanced UC.

Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, developing resistance to cabazitaxel is a major challenge in patients with docetaxel-resistant and castration-resistant prostate cancer (CRPC) because cabazitaxel is often administered as a last resort. However, the mechanism by which cabazitaxel resistance develops is still unclear. C-C motif chemokine ligands (CCL) were shown to contribute to the castration resistance of prostate cancer cells via an autocrine mechanism. Therefore, we focused on CCL as key factors of chemoresistance in prostate cancer cells. We previously established a cabazitaxel-resistant cell line, DU145-TxR/CxR, from a previously established paclitaxel-resistant cell line, DU145-TxR. cDNA microarray analysis revealed that the expression of CCL2 was upregulated in both DU145-TxR and DU145-TxR/CxR cells compared with DU145 cells. The secreted CCL2 protein level in DU145-TxR and DU145-TxR/CxR cells was also higher than in parental DU145 cells. The stimulation of DU145 cells with CCL2 increased the proliferation rate under treatments with cabazitaxel, and a CCR2 (a specific receptor of CCL2) antagonist suppressed the proliferation of DU145-TxR and DU145-TxR/CxR cells under treatments of cabazitaxel. The CCL2-CCR2 axis decreased apoptosis through the inhibition of caspase-3 and poly(ADP-ribose) polymerase (PARP). CCL2 is apparently a key contributor to cabazitaxel resistance in prostate cancer cells. Inhibition of the CCL2-CCR2 axis may be a potential therapeutic strategy against chemoresistant CRPC in combination with cabazitaxel.

Background/aim To evaluate the clinicopathological characteristics and prognosis of squamous cell carcinoma (SCC) of the urinary tract (UT) urothelium, and investigate the utility of perioperative chemotherapy. Patients and methods Thirty-three patients diagnosed with SCC in renal pelvis, ureter and bladder at the Kanazawa University between 2007 and 2017 were included in this retrospective study. Cancer-specific survival (CSS) rates according to cancer stage and neoadjuvant chemotherapy (NAC) were determined. Results Among the entire cohort, two-year CSS rates were 100%, 75%, 47% and 0% in stages I, II, III and IV, respectively, with a significant correlation between CSS and cancer stage (p=0.0063). Sixteen patients underwent radical surgery, and seven patients received NAC; however, there were no significant differences in CSS rates among patients stratified by NAC (p=0.7043). Conclusion Worse cancer stage for SCC of UT urothelium was associated with worse prognosis. Given the poor efficacy of NAC in these patients, surgical treatment should be preferred.

Understanding the mechanism of lymph node metastasis, a poor prognostic sign for prostate cancer, and the further dissemination of the disease is important to develop novel treatment strategies. Recent studies have reported that C-C chemokine receptor 7 (CCR7), whose ligand is CCL21, is abundantly expressed in lymph node metastasis and promotes cancer progression. Tumor necrosis factor-α (TNF-α) is chronically produced at low levels within the tumor microenvironment. The aim of this study was to determine whether TNF-α promotes prostate cancer dissemination from metastatic lymph nodes through activation of the CCL21/CCR7 axis. First, human prostate cancer cells were determined to express both TNF-α and CCR7. Second, low concentrations of TNF-α were confirmed to induce CCR7 in prostate cancer cells through phosphorylation of ERK. Finally, CCL21 was found to promote the migration of prostate cancer cells through phosphorylation of the protein kinase p38. Our results suggest that TNF-α leads to the induction of CCR7 expression and that the CCL21/CCR7 axis might increase the metastatic potential of prostate cancer cells in lymph node metastasis.

Objectives: Prostate cancer (PCa) with lymph node (LN) metastasis has a poor patient prognosis. Broader understanding of the causes of LN metastasis and disease dissemination will assist in developing novel treatments. C-C chemokine receptor 7 (CCR7) and its ligand CCL21 are abundantly expressed in LN metastasis and during PCa progression. Tumor necrosis factor-alpha (TNF-α) is present at low levels within the tumor microenvironment. TNF-α and C-C chemokines interact in tumorigenesis. The study aim was to determine whether TNF-α might promote PCa dissemination from metastatic LN by activating the CCL21/CCR7 axis. Methods: TNF-α and CCR7 mRNA and protein expression were assayed in PC-3, DU145, and LNCaP, and human PCa cells by reverse transcription-polymerase chain reaction and western blotting. Promotion of transmembrane migration by TNF-α was assayed in CCL21-pretreated PCa cells. Phosphorylation of several mitogen-activated protein kinases expressed downstream of TNF-α was assayed. Results: Low-dose TNF-α induced CCR7 expression in PCa cells and promoted migration of CCL21-pretreated PCa cells. TNF-α-mediated CCR7 upregulation via the ERK signaling pathway. p38 was a downstream target of CCL21/CCR7 signaling and a key factor in the promotion of PCa cell migration. Conclusions: This is the first demonstration of the influence of the TNF-α-CCL21/CCR7 axis on PCa cell migration in the microenvironment of LN metastasis. Because it is activated in PCa LN metastasis, the CCL21/CCR7 axis might be a novel therapeutic target and biomarker of PCa. Citation Format: Tomoyuki Makino, Kouji Izumi, Aerken Maolake, Ariunbold Natsagdorj, Hiroaki Iwamoto, Suguru Kadomoto, Renato Naito, Kaoru Hiratsuka, Yoshifumi Kadono, Atsushi Mizokami. Tumor necrosis factor-α upregulation of CCR7 induces prostate cancer cell migration in lymphatic metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1968.