Adenoid Cystic Carcinoma

P1, N=572, Recruiting, Seagen Inc. | N=430 --> 572 | Trial completion date: Jan 2027 --> Nov 2027 | Trial primary completion date: Jun 2025 --> Nov 2027

P2, N=38, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Nov 2024 | Trial primary completion date: Mar 2025 --> Nov 2024

Single-cell RNA sequencing (scRNA-seq) of blood from metastatic ACC identified a cluster of circulating tumor cells (CTCs) expressing MYB. Here, we report a sensitive, cost-effective, and minimally invasive diagnostic test that leverages tumor-specific signatures to screen for metastatic ACC disease, potentially enhancing detection earlier than the current clinical standard.

We show that the majority of salivary gland tumor fusions can be effectively detected with a single rapid NanoString based assay, which can serve as a useful adjunctive tool for routine diagnostic head and neck pathology. The assay is low cost with a rapid turnaround time (30 h total assay time per sample batch, with minimal technician input required) compared to alternate detection methods.

P1, N=14, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

The detection of MYB expression using immunohistochemistry varies significantly depending on the antibody used. Comparison with MYB fusion and transcription levels, as determined by NGS, reveals that MYB has a complex relationship between genetic alterations, transcript levels, and protein abundance.

Accordingly, we achieved a complete response in a radiotherapy (RT) and chemotherapy (CT)-refractory patient with locally recurrent lacrimal gland (LG) ACC and lung metastasis following personalized immunotherapy in combination with integrative therapeutics. Therefore, it is crucial to assess not only conventional immune biomarkers but also patient-specific parameters, especially in "immune-cold" cancer types.

Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

Here, we present a case of high grade ACC lacking NR4A3 gene translocation but harbouring a hitherto undescribed SYN2::PPARG gene fusion of uncertain clinical significance. Clinical, radiological, histological and genomic features of the case are discussed alongside a brief review of the literature.

The identification of characteristic genetic alterations and/or immunohistochemical surrogates in many of these tumors has practical applications to establishing an accurate diagnosis and directing clinical management. This review highlights the histopathologic and genetic characteristics of salivary gland-like breast tumors and the implications of the diagnosis for current clinical management.

P=N/A, N=32, Recruiting, Dana-Farber Cancer Institute | N=66 --> 32

Systemic treatments contribute to the survival of patients with salivary gland cancer at relapsed or newly advanced stages. The response to treatment is heavily influenced by histological subtype and treatment specificity.

Salivary glands' ACC shows imbalance of the MMR complex and loss of expression of its components is associated with the overall survival of these patients.

P2, N=10, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Sep 2024 --> Dec 2024

The trial failed to meet the pre-specified 6-month PFS and BOR targets. We hypothesize that TKI efficacy may be reliant upon an interplay between kinase inhibition and the ACC immune microenvironment, while programs promoting cell cycle progression may contribute to TKI resistance. These observations suggest that trials evaluating CDK4/6 inhibition plus a VEGFR-TKI should be considered.

P2, N=64, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

A novel finding was the discovery of an HMGA2::LINC02389 fusion in 1 patient with EMC ex-PA. The present results indicate that molecular profiling of CXPA with myoepithelial differentiation (MC) tends to reveal chromosomal fusion events, whereas CXPA with epithelial differentiation (SDC) tends to have a higher frequency of pathogenic mutations and gene amplifications.

Overall, we conclude that the presence of Gipie has a confounding role during the ACC-immune cell interaction.

This is the first report of WES analysis of an HMSC, in this case associated with HPV type 35. The detected mutation in EP300 and the overexpression of MYB may serve as molecular targets for personalized therapy.

Adenoid cystic carcinoma arising in the external auditory canal is rare, and even rarer are cases with sebaceous differentiation mimicking sebaceous carcinoma. This case with clinical, radiologic, gross, and histologic images exemplifies an unusual occurrence of adenoid cystic carcinoma in the external auditory canal with sebaceous differentiation, confirmed by MYB::NFIB fusion.

P2, N=5, Enrolling by invitation, Mayo Clinic | Not yet recruiting --> Enrolling by invitation

The tumor cells showed p63 immunoreactivity in basaloid tumor cells and were negative for CD117 and S-100P. This tumor should be differentiated from adenoid basal cell hyperplasia, which has a favorable outcome, and adenoid cystic carcinoma, with a dismal course.

In conclusion, our study demonstrated that TRPS1 is a highly sensitive marker for most special types of breast carcinoma. TRPS1 was positive in 63.73% of apocrine carcinomas. TRPS1 and AR expression was inversely correlated in TNBC.

Also, 1 case with an ESRRG::DNM3 fusion of unknown significance is described in this study. These discoveries illustrate how broad molecular profiling will expand understanding of changes in known entities.

The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune-inflamed type, and this may support the rationale of ICPi for this pathological subtype.

Positive NICD1 expression was associated with worse disease-free survival (hazard ratio, 6.27; 95% CI, 1.29-30.46), whereas positive P63 expression was associated with better disease-free survival (hazard ratio, 0.03; 95% CI, 0.0002-0.26). IHC for NICD1 and P63 should be considered in lacrimal gland ACC because of their prognostic value and potential as treatment targets.

Our findings revealed a novel reciprocal loop between neural and tumor cells driven by the CCL2/CCR2 axis and exosomal ITGβ5 during PNI of SACC. The present study may provide a prospective diagnostic and anti-PNI treatment strategy for SACC patients via targeting the nerve-tumor interactions.

Although MYB protein expression alone lacks diagnostic precision, protein expression >60% predicted the MYB::NFIB fusion in all tumors.

The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets.

P2, N=64, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

In Conclusion, the solid variant (solid portion > 30%), high-grade transformation, and sphenoid sinus involvement are negative prognostic factors for sinonasal AdCC. A high prevalence of MYB::NFIB gene fusion may help to correctly classify diagnostically challenging (e.g. metatypical) cases.

The discovery of TRPC6 in glandular tissue indicates a role in salivary gland function and calcium homeostasis is a basis for further research into its significance for tumor development in adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands. TRPC6 could be used as a target for treatment of these tumors. However, the correlation between TRPC6 and submandibular and lacrimal gland diseases requires further exploration.

This report unveils a potential avenue for targeted therapy for the management of metastatic disease: a patient with ACC who harbored a specific fibroblast growth factor receptor 2 (FGFR-2) mutation and responded significantly to a novel FGFR-2 inhibitor. This finding could pave the way for personalized treatment options for ACC patients with similar genetic alterations. Nevertheless, the use of futibatinib requires further investigation to optimize treatment protocols, including exploring combination therapies, identifying predictive biomarkers for treatment response, and developing strategies to overcome potential resistance.

The present study suggests that the clinicopathological features of ICC are low-grade hormone receptor-positive luminal type with a good prognosis. However, some patients were HER2-positive and require careful follow-up.

P2, N=5, Not yet recruiting, Mayo Clinic

Primary tracheal ACC is most commonly treated with surgical resection followed by adjuvant therapy. Further characterization of the tumor immune microenvironment is necessary to better understand ACC disease biology and to identify potential therapeutic targets.

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2033 --> May 2026 | Trial primary completion date: May 2033 --> May 2026

P1, N=32, Suspended, Groupe Oncologie Radiotherapie Tete et Cou | Recruiting --> Suspended

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> May 2033 | Trial primary completion date: May 2026 --> May 2033

The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4+ T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.

Our study revealed diffuse/strong MYB staining (3+) only in solid/basaloid adenoid cystic carcinomas. Thus, we recommend routine MYB IHC staining in triple-negative breast carcinoma with solid/basaloid morphology to improve diagnostic accuracy.

UM-HACC-14, patient-matching UM-PDX-HACC-14, and the UM-HACC-6 cell line are new, authenticated preclinical models of ACC that are well suited for mechanistic and developmental therapeutics studies.