Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are some indications that the prevalence of benign and malign neoplasms is increased in patients with a mitochondrial disorder (MID). This study aimed at calculating the prevalence of malign and benign neoplasms in MID patients compared to the general population. Among 103 adult patients with definite or probable MID 16 had a malignancy (15.5%) and 11 (10.7%) a benign neoplasm. Four patients had thyroid cancer, three patients had prostate cancer, two patients each colon cancer, or ovarian cancer, and one each lung cancer, basalioma, Paget carcinoma of the skin, Bowen disease, renal cancer, and urinary bladder cancer. One patient had two carcinomas. Five patients had lipomas, two thyroid adenoma, and one each meningeoma, ovarian adenoma, hemangioma of the liver, and pituitary adenoma. Compared to the general population, the prevalence of malignancies was 3-4 fold increased in definite and probable MIDs. Compared to a cohort of myotonic dystrophy type-1 patients, the prevalence was 1.4 fold increased. In conclusion, adult MID patients seem to carry an increased risk to develop malignancy or a benign neoplasm. Females with a MID seem to be predominantly at risk to develop a neoplasm.
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PMID:Prevalence of neoplasms in definite and probable mitochondrial disorders. 2718 Oct 47

Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSCs remains promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSCs and disrupted cancer foci. In addition, we identified mefloquine hydrochloride, an antimalarial drug, as a novel RAB5/7 inhibitor and promising colorectal CSC-targeting drug. Endolysosomal RAB5/7 and LAMP1/2 mediated parkin-dependent mitochondrial clearance and modulated mitophagy through lysosomal dynamics. In a patient-derived xenograft (PDX) model of colon cancer, treatment with mefloquine resulted in suppression of mitophagic PINK1/PARKIN and increased mitochondrial disorder and mitochondria-induced apoptosis without apparent side effects. These results suggest that the combination of mefloquine with chemotherapeutic agents in the PDX model potentially disrupts the hierarchy of colorectal cancer cells and identify endolysosomal RAB5/7 and LAMP1/2 as promising therapeutic targets in CSCs. SIGNIFICANCE: These findings show that endosomal/lysosomal RAB5 and RAB7, which regulate mitophagy, are essential for the survival of colon cancer stem cells.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/7/1426/F1.large.jpg.
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PMID:Disruption of Endolysosomal RAB5/7 Efficiently Eliminates Colorectal Cancer Stem Cells. 3076 2