The 5th Kidney Cancer Research Summit: Research Accelerating Cures for Renal Cell Carcinoma in 2023

Abstract

The 5th Kidney Cancer Research Summit was a hybrid event hosted in Boston, MA in July 2023. As in previous editions, the conference attracted a wide representation of global thought leaders in kidney cancer spanning all stages of clinical and laboratory research. Sessions covered tumor metabolism, novel immune pathways, advances in clinical trials and immunotherapy, and progress toward biomarkers. The abstract presentations were published as a supplement in The Oncologist (https://dbpia.nl.go.kr/oncolo/issue/28/Supplement_1). Aiming to be more concise than comprehensive, this commentary summarizes the most important emerging areas of kidney cancer research discussed and debated among the stakeholders at the conference, with relevant updates that have occurred since.

Introduction

In the US in 2023, kidney cancer diagnoses rose to over 81,000 and caused nearly 15,000 deaths.¹ Over 90% of adult kidney cancers are renal cell carcinoma (RCC), a disease which presents as several subtypes characterized by different histologies, molecular alterations, and clinical outcomes,^2,3 the most common and well studied being clear cell RCC (ccRCC). Despite a plethora of treatment options that have been approved for ccRCC in recent years, current therapies rarely provide complete responses and progression often occurs. Improvements are even scarcer in treating heterogeneous non-clear cell (nccRCC) variants, which pose greater difficultly for conducting clinical trials.

In recent years, kidney cancer research has been championed by the tireless advocacy efforts of patients and their families, contributing to increased funding. The Department of Defense’s Kidney Cancer Research Program (KCRP) began in 2017 as a $10 million program and has grown to $50 million in FY23. In 2019, the non-profit organization KidneyCAN spearheaded creation of a conference to bring together KCRP awardees to discuss their projects with clinical experts and patient advocates. This perspective will focus on selected areas of the RCC research landscape featured at the Kidney Cancer Research Summit (KCRS), as well as relevant updates that have occurred since.⁴

Tumor Molecular Features and Known and Novel Targets

Hypoxia inducible factor (HIF)

The approvals of VEGF inhibitors beginning with sorafenib and sunitinib in 2005 and 2006, respectively, confirmed the validity of angiogenesis as a target in RCC. The development of therapeutic modalities targeting angiogenesis for metastatic RCC led to significant improvements in overall survival (OS).⁵ Standard front-line therapy is now based on combinations of anti-angiogenic tyrosine kinase inhibitors (TKIs) with immune checkpoint inhibitors (ICIs),⁶ including axitinib + pembrolizumab (FDA approved in 2019), lenvatinib + pembrolizumab (2021), and cabozantinib + nivolumab (2021), all resulting in a survival benefit. Next-line treatment options should identify novel therapeutic targets for confronting resistance and potential new combinations with approved drugs.

Oxygen sensing has been a focus of preclinical and clinical studies^7-10 as most ccRCC tumors exhibit biallelic loss of the tumor suppressor gene VHL, which regulates hypoxia signaling.^11,12VHL loss leads to stabilization of the transcription factors HIF-1α and HIF-2α, which induce anaerobic metabolism and tumor growth, respectively. Specifically, HIF-1α acts as a tumor suppressor ccRCC preclinical models; HIF-2α regulates tumor neovasculaturization, metastasis, and antigen presentation in the context of RCC.¹³ The equilibrium between HIF-1α and HIF-2α therefore appears to strongly affect the tumor microenvironment (TME). Recently a conserved 48 gene signature was described for HIF activation in tumor cells including ccRCC.¹⁴

As a key driver of ccRCC tumorigenesis, HIF-2α emerged as a target for drug development. The first HIF-2α drug to reach the clinic, belzutifan is an oral drug that was approved for VHL disease-associated RCC in 2021, and it continues its clinical development in various combinations for advanced RCC.¹⁵ Another oral small-molecule HIF-2α inhibitor, NKT2152, is in early clinical development as a monotherapy or in combination. ARO-HIF2, an RNA interference (RNAi) drug that silences HIF-2α expression, has shown some activity in a phase 1b dose-finding study.¹⁶

Researchers are also investigating mechanisms of resistance to HIF-2α inhibitors, with characterization of HIF2-independent disease both in cell lines and in vivo models of patient-derived tumors. In murine knockout studies, HIF2A deletion favors tumor signatures associated with an active immune system with infiltration by CD8⁺ T cells into the tumor, as well as CD69⁺ cells and perforin.¹³ The absence of HIF-2α also stabilizes the oncogenic tumor growth regulator BRD9,¹⁷ a druggable target which may help patients who have disease that does not respond to HIF-2α inhibitors. Other emerging targets in this context include SFMBT1 and its downstream target SPHK1, as well as ZHX2.^18,19

Lipids and Ferroptosis

Various aspects of RCC tumor metabolism are being interrogated at the preclinical and early clinical stages. Hypoxia-mediated inactivation of lipid storage pathways appears to be a critical step in the development of ccRCC.²⁰ ccRCC tumor cells maintain high intracellular accumulation of cholesterol,²¹ achieved via external import of high-density lipoprotein through the SCARB1 transporter, inhibition of which induces cell-cycle arrest, apoptosis, and elevated reactive oxygen species (ROS) levels.²² Intratumoral heterogeneity in ccRCC appears to be driven by utilization of polyunsaturated fatty acids (PUFAs), cysteine accumulation, and ROS tolerance.²³ These characteristics increase susceptibility to ferroptosis, a form of cell death caused by imbalance in metabolic pathways.²⁴ Ferroptosis is characterized by iron (heme)-dependent oxidation of PUFAs, and dysfunctional repair activity by the phospholipid hydroperoxidase GPX4.

Renal tumors can suppress ferroptosis, leading to cell survival via various pathways that present potential targets. GPX4 expression was shown to be associated with reduced ferroptosis and increased metastasis in mouse models of ccRCC.^25,26 The phospholipase iPLA2β inhibits p53-driven ferroptosis through detoxification of peroxidized membrane lipids.²⁷ In a study of ccRCC samples from The Cancer Genome Atlas database, mRNA expression profiles of ferroptosis-related genes sort into high- and low-expressing subgroups with distinct prognosis and immune cell infiltrations.²⁸ The cluster with the highest ferroptosis score exhibited shorter survival and poorer prognosis, as well as greater presence of immune and stromal cells in the TME. Collectively, these findings highlight the ferroptotic potential of advanced ccRCC tumors that could be a therapeutic strategy.

Strategies to increase ferroptosis have been described. Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a disease characterized by biallelic inactivation of the fumarate hydratase (FH) gene,^29,30 resulting in fumarate accumulation and consequently cysteine methylation. These changes are associated with reduced ferroptosis, but a combination of rapamycin with cysteinase was able to induce ferroptosis in an HLRCC tumor model in vivo.³¹ Obesity, a known risk factor for ccRCC,³² also confers resistance to ferroptosis through increased expression of the adipokine chemerin³³; administration of anti-chemerin antibodies induced ROS and reduced tumor growth in mice.³³ These studies implicate pathways that can reactivate ferroptosis in ccRCC tumors for potential therapeutic modulation, and research into other targets is underway.³⁴

Tumor Microenvironment

Because it is considered a highly immunogenic tumor, immunotherapy has become part of standard front-line treatment strategies for advanced and metastatic ccRCC. These tumors are T-cell enriched, but other immune cell subsets also contribute to the immune microenvironment. Characterization of advanced disease often shows infiltration of terminally exhausted CD8⁺ T cells with restricted T-cell receptor (TCR) diversity, as well as fewer proinflammatory macrophages and increased M2-like macrophages in the myeloid compartment.³⁴ Tumors that respond to ICI demonstrate robust activation and differentiation of these terminally exhausted T cells and a shift toward a pro-inflammatory phenotype in macrophages.³⁵

Myeloid-derived suppressor cells (MDSCs) and M2-like macrophages protect tumor cells against the immune system by downregulating the immune response. IL1β, among other cytokines, is associated to this immunosuppressive state. Anti-IL1β treatment seems to reduce the infiltration of these myeloid cells and may improve response to anti-PD-1 or cabozantinib.³⁶ Furthermore, whole-transcriptomic profiling of localized RCC tumors from the placebo arm of an adjuvant trial showed recurrence associated with expression of myeloid-derived IL6 and TP53 alterations.³⁷ Targeting immunosuppressive tumor resident myeloid cells holds promise for the next phase of systemic therapies.

Animal Models

Preclinical studies in transgenic mouse models of RCC have been hindered because their disease does not represent the human tumors well. Ongoing efforts to develop inducible Cas9 mice that manifest renal tumors have been limited by inability to target multiple driver genes that are located on different chromosomes in the murine versus the human genomes.³⁸ While the fundamental role of VHL inactivation has been extensively studied,^39-41 testing the influence of PBRM1, KEAP1, and TSC1 knockouts in generating murine kidney tumors is ongoing. Loss of 9p21 was shown to be a fundamental event in the evolution of aggressive mesenchymal clones with prominent metastatic behavior in a somatic genetically engineered murine model.⁴²

Greater progress has been made with patient-derived xenograft (PDX) mouse models, which previously contributed to the discovery of the first TME genetic signature in RCC, 2 pan-RCC TME types, and most importantly a link between TME and prognosis.⁴³ Recently a diverse library of 172 stably grafted RCC tumors was reported, generated using samples from 926 individuals over more than a decade.⁴⁴ Although PDX is generated in immunocompromised mice, this platform offers a rich resource for understanding RCC tumor biology, metastasis patterns, and advancing drug development until there are accepted immunocompetent transgenic RCC models.

Distant Metastases

Bone metastases occur in more than a third of patients with advanced RCC⁴⁵ but the mechanism is poorly understood. A time to bone recurrence shorter than 5 years has been associated with worse OS.⁴⁶ RCC bone metastases are resistant to RANKL and PTHrP inhibitors that have proven to be effective in other types of cancer.⁴⁷ RANKL and PTHrP do not seem to be secreted by bone-derived 786-O RCC cells.⁴⁸ BIGH3 mediates the suppression of osteoblast differentiation as a contributing mechanism to the osteolytic effect of RCC in bone,⁴⁸ so therapies targeting osteoblast differentiation are being investigated. Another target of interest is periostin, an osteoblast-specific factor that appears to stimulate migration and invasion in RCC.⁴⁹

Brain metastases from RCC have been associated with high mortality and may be found in ~5% of patients without neurological symptoms.⁵⁰ A retrospective study showed good intracranial activity with cabozantinib,⁵¹ which will be explored prospectively in a phase II trial in this population that is normally excluded from clinical trials (NCT03967522).

Although RCC is considered a radioresistant tumor, radiotherapy may have a facilitating role in systemic therapy by inducing immune activation through increased antigen processing and presentation, as well as tumor sensitization to cytokines. Single-cell analysis showed that in situ irradiated tumors exhibit increased interferon-γ signaling, T-cell clonality, and expression of MUC1, CA9, and MHC class 1 genes.⁵² A prospective trial showed that definitive radiotherapy for patients with previous nephrectomy and <5 metastatic sites is safe and results in promising PFS, accompanied by significant decrease in the proliferation marker Ki-67 in post-radiotherapy biopsies.⁵³ Stereotactic body radiotherapy also showed good outcomes for patients with inoperable localized disease.⁵⁴ Finally, the currently enrolling phase II RADICAL-223 trial compares the combination of Radium-223 and cabozantinib versus cabozantinib monotherapy in patients with bone metastases.⁵⁵

Immunotherapy and Cell Therapies

Immune Checkpoint Inhibitors

Immunotherapy is currently used across treatment settings in RCC. Post-nephrectomy, adjuvant pembrolizumab results in longer disease-free survival compared to placebo in patients at high risk of recurrence^56-58; In advanced RCC, lenvatinib + pembrolizumab yields improved survival outcomes with longer OS and PFS.⁵⁹ MEDI5752, a bispecific antibody that targets both PD-1 and CTLA-4, showed promising activity during a phase I dose-finding study in immunotherapy-naïve patients with RCC, particularly in the first-line treatment setting.⁶⁰ Furthermore, phase III data for the first ICI-based triplet therapy were recently reported.⁶¹

Resistance to PD-(L)1 inhibitors eventually emerges, such that other immune checkpoints are under investigation. LAG-3 expression on tumor-infiltrating immune cells is associated with worse recurrence-free survival and OS, as well as increased immunosuppression due to the presence of exhausted CD8⁺ T cells.⁶² The anti-LAG-3 drug relatlimab was approved as a front-line therapy in melanoma (in combination with nivolumab) based on findings from a phase III trial⁶³ and is under investigation as part of various combinations in RCC. Additional targets are being explored including DC-HIL on MDSC’s, HHLA2/KIR3DL3, and HLA-G/ILT2.^64-66 Future studies will determine which pathways should be developed as the next wave of ICI therapies.

Other Immune Targets

Other active areas of immunotherapy research include the STING pathway, cell therapies, and microbiome manipulation. As part of the innate immune system, STING induces production of type 1 interferon upon sensing cytosolic DNA. Tumor suppressor genes including PBRM1 and BAP1 were proposed to regulate interferon-responsive genes that are also activated by STING agonism.⁶⁷ As these are often co-mutated with VHL in ccRCC oncogenesis this presents a rationale for the continued clinical development of STING agonists, potentially in a biomarker-selected setting. Likewise, ccRCC tumors deficient in NPRL2 (~10%) showed higher rates of immune infiltration and better survival on treatment with ICI, which might be potentiated with inhibitors targeting the G2 checkpoint kinase Wee1 that trigger release of cytosolic DNA.⁶⁸ Telomerase inhibitors could also have an antitumor effect mediated by STING, as telomerase expression is greater in RCC than in adjacent normal tissues.⁶⁹

CAR-T therapies for RCC have begun to emerge past the preclinical space. The allogeneic anti-CD70 CAR-T therapy ALLO-316 recently reported phase I results from 18 patients with advanced or metastatic RCC that had progressed on ICI and VEGF-TKIs with noted activity in CD70⁺ tumors.⁷⁰ The anti-CD70 CAR-T therapy CTX130 has led to a durable complete response in a patient with refractory disease in an early study.⁷¹ Bispecific CAR-Ts being developed against both CD70 and CAIX are hoped to achieve greater specificity of the induced immune response toward RCC cells.⁷² More experimental cell therapies should appear in coming years, driven by intense interest in determining how to balance safety and efficacy of these powerful treatments in solid tumors.

The potential of microbiome-centered interventions to augment immunotherapy is an area of vigorous translational and clinical development.⁷³ Taxonomic and functional profiling of the gut microbiome could help identify commensals associated with response to ICIs, and there are already some promising leads. Adding the live bacterial product CBM588 (Clostridium butyricum), an oral probiotic at 80 mg twice daily, to nivolumab with ipilimumab or cabozantinib conferred a PFS advantage in patients with metastatic RCC in 2 small randomized studies.⁷⁴ The complicated mechanism of action might involve increasing certain chemokines.

Predictive Biomarkers

Given the position of immunotherapy as a standard front-line choice in RCC, attention has focused on identification of biomarkers that would allow prediction of which patients are likely to benefit from that therapy, to decrease both cost and risk of toxicity for patients unlikely to benefit. In this context, immune cytokines have a proven association to treatment response.^75,76 A prospective analysis showed that lower pretreatment IL-6, IL1RA, and GCSF were associated with clinical benefit on VEGF-TKI, but had no effect on response to ICI; a greater increase of IFN-γ and IL-12 while on ICI was associated with response.⁷⁷ AXL is a receptor tyrosine kinase that is often co-expressed with PD-L1 and correlates with shorter survival in patients treated with nivolumab after failure of antiangiogenic therapy.⁷⁸ Using immunofluorescence on tumor pathology samples, CD8⁺ TILs that are PD-1⁺TIM-3⁻LAG-3⁻ are associated with longer median PFS and enhanced ORR with nivolumab⁷⁹ and, along with expression of the human endogenous retrovirus ERVE-4, associated with better clinical outcomes.⁸⁰ In the RCC cohort (n = 24) of the Hope111 phase II trial of lenvatinib + pembrolizumab, germline HLA-I diversity was predictive of clinical benefit, and validated in an independent cohort (n = 41) of patients treated with ICI combination therapy.⁸¹

Multiplex and/or multimodality signatures are more likely to predict immunotherapy outcomes than unidimensional biomarkers. One method that might be inexpensive and widely applied is combining tissue staining of TILs with necrosis scoring, which was able to predict stratified OS on pre-immunotherapy RCC tumor tissue samples and was further improved when PBRM1 mutational status was known.⁸² In the IMmotion151 phase III trial of atezolizumab + bevacizumab versus sunitinib, unsupervised multi-omic characterization produced 7 molecular clusters derived from 823 tumor samples, demonstrating distinct PFS⁸³ and OS⁸⁴ differences that merited cross-trial validation. When the molecular clusters were applied to the JAVELIN Renal 101 phase III trial of axitinib + avelumab versus sunitinib, although distribution of the clusters was largely similar, both ORR and PFS favored the intervention arm across all clusters.⁸⁵

Cell-free tumor DNA (ctDNA) is a minimally invasive liquid biopsy that can be performed at several timepoints, and accounts for tumor heterogeneity as it sheds from both primary and metastatic sites.⁸⁶ ctDNA was detected in 71.8% of 920 samples from patients with mRCC, and many mutations identified in tissue were also seen in the ctDNA and vice versa.⁸⁷ A clinical trial that aims to monitor ctDNA in patients with mRCC receiving immunotherapy is currently underway (NCT04883827).

Going forward, it will be important to validate all promising biomarkers prospectively in randomized trials, especially with immunotherapy now being used as a comparator arm in contemporary studies. One such trial, the phase II OPTIC RCC,⁸⁸ engages a machine-learning model trained on the IMmotion151 dataset to assign patients, based on their RNA-seq results, to receive either nivolumab + ipilimumab or nivolumab + cabozantinib (NCT05361720).

Variant Histologies of RCC

Roughly a quarter of all RCC tumors harbor diverse histologic subtypes with different molecular and clinical characteristics, termed non-clear cell RCC (nccRCC). The microenvironment of some nccRCC subtypes has been described, with CD8⁺LAG-3⁺ T cells playing a central role in exhaustion.⁸⁹ As HAVCR2/LAG-3 is upregulated in nccRCC-derived macrophages as well, LAG-3 could be a better therapeutic target than PD-(L)1. Deepening our knowledge of nccRCC biology in individual subtypes is a necessary step to treatment optimization, but some progress is being reported clinically with a phase II study of lenvatinib + everolimus in the first-line yielding 26% ORR for pooled nccRCC (n = 31); the highest ORR (4/9, 44%) was seen in chromophobe RCC.⁹⁰ A phase Ib study showed promising results for cabozantinib + atezolizumab with a 31% ORR (n = 32).⁹¹ The relative rarity of individual nccRCC subtypes presents an inherent difficulty for conducting sufficiently powered clinical trials in this space.

Papillary RCC (pRCC) constitutes 15% of all RCC and is itself a heterogeneous tumor with mixed features in a spectrum of histological entities.⁹² While pRCC usually originates from proximal tubule cells, it can also arise from collecting duct principal cells.⁹³ Differences in cell-of-origin underlie molecular, clinical, and therapeutic variation, and contributes to tumor complexity. The TME of pRCC shows high levels of CD68, a macrophage marker.⁹⁴ Some samples exhibit lower levels of markers for lymphocyte infiltration (CD8, CD20) and aggressiveness (CD31, Ki67). TME composition also correlates to clinical outcomes.⁹⁵ As pRCC often presents with somatic and germline MET alterations,⁹⁶ a phase II trial tested 3 MET kinase inhibitors vs. sunitinib in 152 patients with metastatic disease; 10 patients on cabozantinib (23%) experienced tumor shrinkage, with 1 CR.⁹⁷ Newer MET inhibitors in development will hopefully offer greater benefit.^98,99

Arising from intercalated cells of the distal nephron, chromophobe RCC (chRCC) tends to present as more indolent than ccRCC, but at advanced stages response to both targeted therapy and immunotherapy is dismal. Single-cell studies indicate the tumor is poorly infiltrated by lymphocytes, and that they do not express exhaustion markers, explaining the lack of response of chRCC to ICI.¹⁰⁰ Metabolic profiling showed high levels of glutathione, over 100 times higher than in normal kidney.^101,102 These metabolic characteristics make chRCC cells hypersensitive to induction of ferroptosis, which is being further explored preclinically for therapeutic implications.¹⁰³

Translocation RCC (tRCC) is an aggressive form of kidney cancer driven by Mit/TFE gene fusions, and predominantly affects children.^104,105 While histologically heterogeneous, tRCC tumors consistently express high levels of NRF2 despite few genetic alterations in this pathway, which putatively confers resistance to targeted therapies.¹⁰⁶ ICIs in combination with agents targeting the NRF2 pathway should be explored to improve responses.

Renal medullary carcinoma (RMC) affects mostly adolescents and young adults of African descent. It is also associated with hemoglobinopathies,¹⁰⁷ and high-intensity exercise in patients with sickle cell disease has been shown to be a modifiable risk factor.¹⁰⁸ Highly lethal, RMC is currently treated with platinum-based chemotherapy. The particularities of its immune microenvironment suggest resistance to immunotherapies, but proteasome inhibitors could be effective in this setting by suppressing hypoxia-induced degradation of the tumor suppressor SMARCB1.^109,110

Conclusion

Following its 5th edition, KCRS has continued to benefit from the exchanges between translational scientists, clinical practitioners, basic scientists, and well-informed patient advocates. Practical aspects of care and clinical development are also addressed, such as how to modernize practice patterns outside of comprehensive cancer centers (single-agent TKIs are still often prescribed), and design of clinical trials with appropriate comparator arms and enrollment of diverse patient populations. The kidney cancer field must keep these factors in perspective while endeavoring to better understand and therapeutically exploit the biology of RCC for the evolving benefit of patients suffering with this disease.

Conflict of Interest

Toni K. Choueiri has received support for the present manuscript: Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infiniti, Ipsen, Kanaph, Lilly, Merck, Nikang, Novartis, NuScan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (PeerView, PER, MJH Life Sciences, Research to Practice, France Foundation, Springer, WebMed, ASiM CE, Caribou Publishing); research funding related to clinical trials (institutional): AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Lilly, Merck, Nikang, Novartis, Pfizer, Roche, Sanofi/Aventis, Takeda; consulting fees (personal, outside related work): AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infiniti, Ipsen, Kanaph, Lilly, Merck, Nikang, Novartis, NuScan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (PeerView, PER, MJH Life Sciences, Research to Practice, France Foundation, Springer, WebMed, ASiM CE, Caribou Publishing); honoraria for lectures, presentations, manuscript writing, or educational events (personal): AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infiniti, Ipsen, Kanaph, Lilly, Merck, Nikang, Novartis, Pfizer, Roche, Sanofi/Aventis, Takeda, Tempest, Up-To-Date, CME events (PeerView, PER, MJH Life Sciences, Research to Practice, France Foundation, Springer, WebMed, ASiM CE, Caribou Publishing); support for attending meetings and/or travel (personal); has patents planned, issued or pending related to ctDNA and biomarkers of response to immune checkpoint inhibitors (no royalties as of April 12, 2022); participated on a data safety monitoring board or advisory board (personal, outside related work): Aravive; has a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid (personal, outside related work): KidneyCAN (unpaid), Committees for ASCO/ESMO/NCCN/GU Steering Committee of the NCI; owns stock or stock options (personal, outside related work): Pionyr, Tempest, Precede Bio, Osel; is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan-Mass Challenge, Hinda and Arthur Marcus Fund and Loker Pinard Funds for Kidney Cancer Research at DFCI. Sumanta K. Pal has received travel support from CRISPR Therapeutics and Ipsen. Bryan Lewis is President and co-founder of KidneyCAN and has no other declarations related to the present work. Susan Poteat is an employee of KidneyCAN and has no other declarations related to the present work. Kevin Pels has no declarations related to the present work. Hans J. Hammers has acted as a paid consultant for and/or as a member of the advisory boards of Exelixis, BMS, Pfizer, Merck, Corvus, Armo Biosciences, Eisai, Eli Lilly, Surface Oncology, Aveo and Novartis; has received grants to his institution from Merck, Bristol-Myers Squibb, Surface Oncology and Aravive for work performed as outside of the current study; and is a member of the Board of Directors of KidneyCAN.

References