More focus on cancer STEM cells

Dr. Weeks’ Comment: Stop already, the targeting and killing of cancer TUMOR cells with chemo and radiation and instead target the cancer STEM cells with once-immunology and anti-inflammatory agents. Corrective Cancer Care™ is the future. Be informed. Get educated.  Chemo and radiation make your cancer WORSE  by stimulating the lethal cancer STEM cells to be more numerous and more virulent. 

 

Salivary gland cancer patient-derived xenografts enable characterization of cancer stem cells and new gene fusions associated with tumor progression

Stephen KeysarJustin EaglesBettina MillerBrian C JacksonFarshad N ChowdhuryJulie ReisingerTugs-Saikhan ChimedPhuong N. LeJ. Jason MortonHilary SomersetMarileila Varella-GarciaAik-Choon TanJohn I. SongDaniel W. BowlesMary E. Reyland and Antonio Jimeno

Abstract

Purpose: Salivary gland cancers (SGC) frequently present with distant metastases many years after diagnosis, suggesting a cancer stem cell (CSC) subpopulation that initiates late recurrences; however current models are limited both in their availability and suitability to characterize these rare cells.

Experimental Design: Patient-derived xenografts (PDX) were generated by engrafting patient tissue onto nude mice from one acinic cell carcinoma (AciCC), four adenoid cystic carcinoma (ACC), and three mucoepidermoid carcinoma (MEC) cases, which were derived from successive relapses from the same MEC patient. Patient and PDX samples were analyzed by RNA-seq and Exome-seq. Sphere formation potential and in vivo tumorigenicity was assessed by sorting for Aldefluor (ALDH) activity and CD44 expressing subpopulations. Results: For successive MEC relapses we found a time-dependent increase in CSCs (ALDH+CD44high), increasing from 0.2% to 4.5% (P=0.033), but more importantly we observed an increase in individual CSC sphere formation and tumorigenic potential. A 50% increase in mutational burden was documented in subsequent MEC tumors, and this was associated with increased expression of tumor promoting genes (MT1E, LGR5, LEF1), decreased expression of tumor suppressor genes (CDKN2B, SIK1, TP53), and higher expression of CSC-related proteins such as SOX2, MYC, and ALDH1A1.

Finally, genomic analyses identified a novel NFIB-MTFR2 fusion in an ACC tumor and confirmed previously reported fusions (NTRK3-ETV6 and MYB-NFIB).

Conclusions: Sequential MEC PDX models preserved key patient features and enabled the identification of genetic events putatively contributing to increases in both CSC proportion and intrinsic tumorigenicity, which mirrored the patient’s clinical course.

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Dr. Weeks’ Comment: Stop already, the targeting and killing of cancer TUMOR cells with chemo and radiation and instead target the cancer STEM cells with once-immunology and anti-inflammatory agents. Corrective Cancer Care™ is the future. Be informed. Get educated.  Chemo and radiation make your cancer WORSE  by stimulating the lethal cancer STEM cells to be…
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