DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for clear cell adenocarcinoma — screening already-approved drugs against its 28-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleClear cell adenocarcinoma maps to a 28-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for clear cell adenocarcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
Bruton tyrosine kinase (BTK) — BTK is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 7h-pyrrolo[2,3-d]pyrimidin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6VXQ · 1.4 Å · ligand N-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl}benzamide (RQS). Experimental structure, not a prediction.
What the evidence adds up to
In 1997, researchers studied 13 permanent human renal cell carcinoma cell lines of the clear cell type. All cell lines expressed EGF-receptor mRNA and protein, and 10 lines secreted TGF-alpha. Exogenous TGF-alpha significantly stimulated growth in 6 cell lines and significantly inhibited proliferation in 3. Eleven cell lines expressed TGF-beta 1 mRNA, and all secreted TGF-beta 1. Exogenous TGF-beta 1 significantly inhibited proliferation in 7 cell lines. The authors concluded that clear cell RCCs exhibit a complex and heterogeneous expression pattern for various growth factors and their receptors.
A 1997 case report described an 8-year-old girl with invasive clear cell adenocarcinoma of the cervix who had not been exposed prenatally to diethylstilbestrol. The report discussed the unique therapeutic considerations in such a paediatric case, including the need for less mutilating surgery and preservation of future fertility, but provided no treatment outcome data.
A 2024 narrative review noted that advances in non-clear cell RCC have lagged behind clear cell RCC. In the studies discussed, no histology enrolled more than 29 patients of any particular RCC aside from papillary. The review stated that clinical response to VEGF-TKIs and immune checkpoint inhibitors varies greatly by histology, and that most data come from single-arm phase 2 trials.
The 2021 ORACLE study retrospectively analysed 66 patients with metastatic non-clear cell RCC who received novel combination therapies. Histologies included papillary (38%), chromophobe (17%), unclassified (24%), translocation (12%), and other (9%). 67% received combination treatment in the first line. The authors reported that response rates and survival with combination therapy in this dataset remained inferior to rates seen in clear cell RCC. A 2023 case report described a 0.6 cm colonic clear cell adenocarcinoma of intestinal-type that was de novo without an adenoma component. The tumour did not have deep submucosal invasion or cancer embolus, and endoscopic submucosal dissection with regular follow-up was considered appropriate. The authors stated that the cause of clear cytoplasm change and the impact on prognosis remain unknown.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 1997 · 38 citations
Functional Intactness of Stimulatory and Inhibitory Autocrine Loops in Human Renal Carcinoma Cell Lines of the Clear Cell Type
AbstractPURPOSE: The aim of the present study was to analyze the contribution of different stimulatory and inhibitory growth factors to the deregulated proliferation of human RCCs. MATERIALS AND METHODS: The expression of different growth factors and their corresponding receptors were analyzed by Northern blot, FACS, ELISA and immunocytochemistry in 13 permanent human RCC cell lines of the clear cell type. Moreover, the functional intactness of growth factor-related signal transduction pathways was investigated. RESULTS: All RCC cell lines expressed EGF-receptor mRNA and protein and 10 cell lines secreted TGF-alpha. Exogeneously added TGF-alpha resulted in a significant (p < 0.05) stimulation of growth in 6 RCC cell lines and a significant (p < 0.05) inhibition of proliferation in 3 cell lines. PDGF B and the corresponding type beta receptor were expressed in a single cell line. mRNA expression of PDGF A and PDGF-alpha-receptor as well as IGF-1 and its receptor could not be detected in any cell line. Eleven RCC cell lines expressed TGF-beta 1 mRNA and in all cell lines TGF-beta 1 secretion into the supernatant could be demonstrated. Whereas all cell lines exhibited TGF-beta type II-receptor mRNA, type I-receptor mRNA could be detected only in 3 cell lines. TGF-beta type III-receptor was observed in 1 cell line. Exogeneously added TGF-beta1 resulted in a significant (p < 0.05) inhibition of proliferation in 7 RCC cell lines. CONCLUSION: Clear cell RCCs exhibit a complex and heterogeneous expression pattern for various growth factors and their receptors. Growth factor secretion and intact signal transduction pathways in most clear cell RCCs facilitate an intricate modulation of RCC growth by autocrine and paracrine interactions between tumor cells and host tissue.
Diagnostic Pathology · 2019 · 14 citations · open access
Colon adenoma and adenocarcinoma with clear cell components - two case reports
AbstractBACKGROUND: Diagnoses reflect clear cell morphologies when tumor cells have clear cytoplasm in many organs, and the nature of such clear cells is typically identified. Colorectal tubular adenoma or adenocarcinoma, conversely, rarely show clear cells, the reason for which remains uncertain. We report 2 colon tumors with clear cell components (Case 1: adenoma; Case 2: adenocarcinoma) and investigate the nature of the clear cells. CASE PRESENTATION: Case 1 was a 75-year-old man with a superficial elevated polyp detected in the rectum for whom endoscopic submucosal dissection was performed. Microscopically, 10% of the tumor showed dysplastic columnar epithelium with clear cytoplasm forming tubular structures accompanied by conventional tubular adenoma. Case 2 was a 58-year-old man with a pedunculated polyp found in his sigmoid colon for which polypectomy was performed. Microscopically, 90% of the tumor showed dysplastic columnar epithelium with clear cytoplasm forming fused glands or cribriform structures adjacent to the ordinal tubular adenocarcinoma. In both cases, clear and ordinary tumor cells were negative for CK7 and positive for CK20 and CDX2, consistent with findings of colorectal origin. Different results were found for CEA and CD10 staining. CEA was positive on the luminal side of the conventional area in contrast diffuse cytoplasmic staining of the clear cell area in both cases. CD10 was only positive for the clear cell component of case 2. The clear cell components were negative for Periodic acid-Schiff (PAS), Alcian blue, and mucicarmine staining and AFP immunohistochemistry. An ultrastructural examination found multiple cytoplasmic lipid-like vacuoles in the clear cell component that were predominantly negative for adipophilin by immunoelectron microscopy. CONCLUSIONS: We investigated tubular adenoma and tubular adenocarcinoma with clear cell components. The accompanying conventional tubular adenoma or adenocarcinoma cells helped us to evaluate the atypia of the clear cells. Diffuse cytoplasmic staining of CEA and CD10 suggested that the clear cell component might harbor malignant potential. We were unable to verify the well-known causes of clear cytoplasm, such as an accumulation of glycogen, lipid, or mucin and enteroblastic differentiation. The causes of clear cells in the colorectal region remain uncertain; however, possible explanations include autolysis and carbohydrate elution.
Asia-Pacific Journal of Clinical Oncology · 2015 · 8 citations · open access
Safety and efficacy of sunitinib for advanced non‐clear cell renal cell carcinoma
AbstractAIM: This study evaluated the safety and efficacy of sunitinib in the treatment of advanced non-clear cell renal cell carcinoma. METHODS: Thirty-seven Chinese patients with advanced non-clear cell renal cell carcinoma were enrolled from October 2008 to October 2013. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral administration of 50 mg for 4 weeks, followed by 2 weeks off. Computed tomography scan was used to evaluate the efficacy every two cycles. RESULTS: All 37 patients received sunitinib treatment according to the schedule and were evaluated for response and toxicity. Thirty (81.1%) patients underwent nephrectomy before sunitinib treatment and seven (18.9%) patients had kidney biopsy. Twenty-five patients were diagnosed with papillary renal cell carcinoma, two with spindle cell-type renal cell carcinoma, two with chromophobe renal cell carcinoma and eight with unclassified cell types. The disease control rate was 73.0%, with partial response in 5 (13.5%), stable disease in 22 (59.5%) and progression disease in 10 (27.0%), the best tumor response. The median progression-free survival (PFS) was 6 months and the median overall survival (OS) was 9 months. In patients with papillary renal cell carcinoma, the median PFS was 6 months and the median OS was 10 months. The most common adverse events were hand-foot syndrome, fatigue, leukopenia, anemia, thrombocytopenia, mucositis, edema and hypertension. All adverse events were ameliorated by supportive treatment, dose reduction or treatment interruption. CONCLUSION: Sunitinib was efficacious in the treatment of advanced non-clear cell renal cell carcinoma. Most adverse events were tolerable.
Hematology/Oncology and Stem Cell Therapy · 2010 · 7 citations · open access
Borderline clear cell adenofibroma with extensive hemorrhagic necrosis
AbstractBorderline clear cell adenofibroma of the ovary is rather rare since most of clear cell tumors are carcinomas. We report a case of ovarian borderline clear cell adenofibroma in a 52-year-old postmenopausal woman. The tumor had the characteristic histologic features of borderline clear cell adenofibroma except for central extensive hemorrhagic necrosis. The prognosis of borderline clear cell adenofibroma is excellent. Because the invasiveness cannot be assessed in the necrotic areas, our patient needed long-term follow-up.
Journal of Gynecologic Surgery · 1997 · 6 citations
Therapeutic Considerations in an 8-Year-old Girl with Clear Cell Adenocarcinoma of the Cervix
AbstractInvasive clear cell adenocarcinoma in the adult is difficult to manage, and in the pediatric population, it presents extremely challenging therapeutic considerations, including decreased long-term morbidity for patients who, when cured, have life expectancies measured in decades. Consequently, less mutilating surgery, improved functional and cosmetic results, and desired future fertility of the patient must be considered. This case report discusses invasive clear cell adenocarcinoma of the cervix in an 8-year-old girl not exposed prenatally to diethylstilbestrol and the unique considerations in therapeutic management. (J GYNECOL SURG 13:31, 1997)
Translational Cancer Research · 2024 · 5 citations · open access
Non-clear cell renal cell carcinoma narrative review: where we are in 2024
AbstractBackground and Objective: Advances in non-clear cell renal cell carcinoma (RCC) have lagged behind clear cell RCC due to the heterogeneity and relative rarity of the disease. However, more advanced molecular and genetic testing has allowed us to gain a more detailed and nuanced appreciation of these malignancies. This has laid the foundation for the identification of the distinct mutational and molecular patterns such as succinate dehydrogenase (SDH)-deficient RCC, fumarate hydratase (FH)-deficient RCC, and translocation RCC, so that clinicians can create a more personalized approach to their clinical management. Particularly for the rare non-papillary RCC variant histologies, clinical trial representation is lacking. In the discussed studies, no histology enrolled more than 29 patients of any particular RCC aside from Papillary. As such, evidence-based management decisions can be challenging to make for this patient population. Methods: We have collected the most up-to-date available evidence to describe the pathophysiology, molecular, and pathologic characteristics of the more commonly seen non-clear cell RCC variants, including papillary, chromophobe, translocation, FH-deficient, as well as a group of "unclassified" RCCs. Additionally, we provide an overview of the available evidence from recent clinical trials for non-clear cell RCC and current treatment paradigms. Key Content and Findings: The diagnostic approach for renal malignancies is rapidly changing, favoring a more molecular and genetically based approach. These techniques will allow for a more detailed understanding of the clinical behavior of these cancers. Most data for non-clear cell RCC are from single-arm phase 2 clinical trials. The clinical response to vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) varies greatly by histology. Conclusions: Molecularly targeted therapy as monotherapy or when combined with immunotherapy have efficacy in non-clear cell RCC, though there are differences in treatment response by histology.
Outcomes with novel combinations in non-clear cell renal cell carcinoma(nccRCC): ORACLE study.
Abstract4580 Background: Despite advances in the treatment of clear cell RCC, there is a paucity of data to guide management of nccRCC due to the heterogeneity and rarity of these tumors. The clinical activity of new combination therapies (including immunotherapy (IO), anti-vascular endothelial growth factor inhibitors (VEGF), and mammalian target of rapamycin (mTOR) inhibitors) in metastatic nccRCC is not known. Methods: In this multicenter retrospective analysis, we explored the efficacy of combination systemic therapies in patients with nccRCC. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate (ORR) assessed by investigator review. Secondary endpoints include progression- free survival (PFS), disease control rate (DCR), median duration of response (DOR), overall survival (OS), and biomarker correlates. Results: Among 66 included patients, median age was 59 yr; 60% were male and 62% white. Histologies included papillary (38%), chromophobe (17%), unclassified (24%), translocation (12%), and other (9 %). Sarcomatoid and/or rhabdoid differentiation was present in 18%, 70% had prior nephrectomy, 86% were IMDC intermediate/poor risk, 29% and 32% had liver and bone metastasis respectively. 67% received combination treatment in the first line. Comparison of outcomes based on treatment regimen is shown in the table. Conclusions: Antitumor activity was observed with novel combinations in nccRCC which warrants further prospective studies. Response rates and survival with combination therapy in this dataset remain inferior to rates seen in clear cell RCC.[Table: see text]
International Journal of Surgical Pathology · 2023 · 1 citations · open access
Colonic <i>de novo</i> Clear Cell Adenocarcinoma of Intestinal-Type: A Case Report and Review of the Literature
AbstractColorectal clear cell adenocarcinomas are rare tumors. They can be divided into two types: intestinal- and Müllerian-type. Most intestinal-type clear cell adenocarcinomas show a composite morphology, and most early-stage (T1) intestinal-type clear cell adenocarcinomas have an adenoma component. We report an additional early-stage (T1) colonic clear cell adenocarcinoma that was a de novo adenocarcinoma without any adenoma component. It had a pure morphology and the smallest size (0.6 cm) ever reported. Immunohistochemical results demonstrated an intestinal phenotype (KRT20+, KRT7−, CEA+, and CDX2+). Periodic acid-schiff and alcian blue stains were both negative, which demonstrated decrease in mucin expression in the clear tumor cells. Enteroblastic differentiation was observed in a few colorectal clear cell adenocarcinomas in the literature, while it had not been observed in the present tumor. The tumor did not have deep submucosal invasion and cancer embolus, endoscopic submucosal dissection with regular follow-up was an appropriate treatment for the patient. Due to the rarity and diversity of primary colorectal clear cell adenocarcinomas, the cause of clear cytoplasm change and the impact on patient prognosis remain unknown. Accumulating evidence indicates that clear cell adenocarcinomas of intestinal-type is a histological variant of colorectal adenocarcinoma.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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