Adenoid Cystic Carcinoma

IκB kinase complex signaling axis in adenoid cystic carcinoma

Curcumin concentration-dependently inhibited the growth of ACC cells via induction of apoptosis. The ability of ACC cells to migrate/invade and induce angiogenesis was also significantly attenuated by curcumin, accompanied by the down-regulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 and -9. Moreover, our data also demonstrated that the inhibitory effects of curcumin on ACC cells were due to its dual inhibition of both mammalian target of rapamycin (mTOR) and nuclear factor-κB (NF-κB) pathways through a crossed phosphatidylinositol 3-kinase/Akt/IκBα kinase signaling axis. Most importantly, curcumin effectively prevented the in vivo growth and angiogenesis of ACC xenografts in nude mice, as revealed by the induction of cell apoptosis and reduction of microvessel density in tumor tissues.

Potential targets identified in adenoid cystic carcinoma point out new directions for further research

The purpose of this research was to identify key genes related to AdCC for further investigation of their diagnostic and prognostic significance. A total of 115 DEGs (differentially expressed genes) were obtained by screening with GEO2R and FunRich software. According to functional annotation analysis using Enrichr, these DEGs were mainly enriched in the SOX2, AR, SMAD and MAPK signaling pathways.

A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that ITGA9, LAMB1 and BAMBI were associated with the PI3K-Akt and TGF-β pathways. The involved pathways, biological processes and miRNAs have been shown to play significant roles in the genesis, growth, invasion and metastasis of AdCC. In this study, these identified DEGs were considered to have a potential influence on AdCC but have not been studied in this disease. ST3Gal4 is a pivotal component of the PPI (protein-protein interaction) network of all the DEGs (Differentially expressed genes) obtained.

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Results: Recent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published that may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare.

Management of adenoid cystic carcinoma of the head and neck: a single-institute study with over 25-year follow-up

Overall 10-year, 20-year, and 25-year survivals were 63.7, 27.3, and 20.0%, respectively. Similarly, disease-specific survival (DSSs) was 65.7, 51.2, and 38.4%, respectively, and disease-free survival was 25.2, 9.4, and 9.4%, respectively. Conducting surgery (HR: 0.19, 95% CI: 0.06-0.61, p = 0.005) and C-T type (HR: 0.32, 95% CI: 0.11-0.93, p = 0.036) were independent prognostic predictors of DSS. DSS was significantly prolonged after salvage surgery for both locoregional recurrence (p = 0.004) and lung metastatic recurrence (p = 0.012, vs best supportive care).

In ACC cases, both initial surgical treatment and repetitive surgical resection of resectable recurrent lesions, including both locoregional and lung metastases, resulted in longer survival. The major goal of treatment for ACC may be long-term survival including cancer-bearing survival, resulting in either natural death or intercurrent-disease death, since judging cure of ACC is almost impossible.

Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review

Once metastatic, the natural history can vary; some patients with indolent cancer remain asymptomatic for long periods, whereas others have rapidly progressive disease. Chemotherapy is generally reserved for the palliative treatment of symptomatic locally recurrent or metastatic disease that is not amenable to further surgery or radiation. Prospective trials of chemotherapy in advanced ACC are limited, and the optimum regimen is unclear.

Head and neck adenoid cystic carcinoma: A prospective multicenter REFCOR study of 95 cases

(Full text)

Results: Mean follow-up was 18 months. On univariate analysis, disease-free survival correlated with T stage (P=0.05), N stage (P=0.003), resection margins (P=0.04), lymph node involvement on histology (P=0.01), and absence of chemotherapy (P=0.03). On multivariate analysis, disease-free survival correlated with T stage (P=0.01), N stage (P=0.09) and surgery (P=0.005).

Conclusion: The essential issue in adenoid cystic carcinoma is long-term control. The present results confirm that the reference attitude is radical surgical resection for optimal local control. Adjuvant radiation therapy did not emerge as a prognostic factor. This study also provides a starting-point for translational studies in pathology and genetics.

Phase II Study of Lenvatinib in Patients With Progressive, Recurrent or Metastatic Adenoid Cystic Carcinoma

Full text

Thirty-three patients were enrolled; 32 were evaluable for the primary end point. Five patients (15.6%) had a confirmed partial response, 24 patients (75%) had stable disease, two patients (6.3%) discontinued treatment as a result of toxicity before the first scan, and one patient (3.1%) had progression of disease as best response. Median progression-free survival time was 17.5 months (95% CI, 7.2 months to not reached), although only eight progression events were observed. Patients otherwise were removed for toxicity (n = 5), as a result of withdrawal of consent (n = 9), or at the treating physician’s discretion (n = 6). Twenty-three patients required at least one dose modification, and 18 of 32 patients discontinued lenvatinib for drug-related issues. The most common grade 3 or 4 adverse events were hypertension (n = 9; 28.1%) and oral pain (n = 3; 9.4%). Three grade 4 adverse events were observed (myocardial infarction, n = 1; posterior reversible encephalopathy syndrome, n = 1; and intracranial hemorrhage, n = 1).

Conclusion: This trial met the prespecified overall response rate primary end point, demonstrating antitumor activity with lenvatinib in R/M ACC patients. Toxicity was comparable to previous studies, requiring monitoring and management.

Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma

Lots of conflicts of interest

[Adenoid cystic carcinoma of the head and neck: a retrospective series of 169 cases]

Mean follow up was about 5 years (58 months).

Radiotherapy did not impact survival.

The value of MYB as a prognostic marker for adenoid cystic carcinoma: Meta-analysis

The current studies reveal that MYB is not a good prognostic marker for ACC.

[Clinicopathological features and prognostic factors of primary pulmonary adenoid cystic carcinoma: a study of 59 cases]

Majority of the patients with primary pulmonary adenoid cystic carcinoma are at an early clinical stage with a favorable prognosis. The size of the tumor and the age of the patients are independent prognostic indicators.

From Jodi Ledley's website, AdventuresWithJodi.com:

MAPK– Overexpressed in many cancers. It regulates gene expression, cell growth and survival. Increased MAPK signaling leads to uncontrolled cell proliferation and resistance to apoptosis (cell death). The substances below inhibit MAPK expression.

EGCG (Green Tea)
Berberine
I3C (Broccoli Sprouts)

MTOR– is often overexpressed in colorectal cancer. Mtor overexpression drives cancer cell growth and angiogenesis. The substances below inhibit mTOR.

Eliminate animal products
Curcumin
EGCG (Green Tea
Resveratrol (Grapes)
Luteolin (Radicchio, Carrots)
Apigenin (Celery)
Quercetin
Indol-3 (Broccoli Sprouts)
Berberine (Supplement)
Black Seed Oil
Garlic

TGF-Beta-is a tumor suppressor gene. When activated it decreases proliferation of cancer cells and increases cancer cell death (apoptosis). The substances below activate TGF-Beta.

Apigenin-POTENT (Celery)
Luetolin (carrots or radicchio)
Quercetin
Vitamin C
I3C (Broccoli Sprouts)
Berberine (Supplement)
Black Seed Oil
Garlic

VEGF (Vascular Endothelial Growth factor) is often overexpressed in cancer. VEGF stimulates vascular (blood vessels to tumor) cell growth, survival, and proliferation.

Burdock root-POTENT (Essiac Tea)
Artemisinin
EGCG (Green Tea)
Apigenin (Celery)
I3C and Sulforaphane (Broccoli Sprouts)