tumor_recurrence

Tumor recurrence

Glioma stem cells (GSC) contribute to the tumor’s heterogenous nature, therapeutic resistance, and, thereby, inevitable tumor recurrence 1) 2).

Ancillary criteria to identify tumor recurrence such as MacDonald criteria or RANO criteria may provide false diagnoses. Perfusion MRI imaging has been proposed to differentiate post-treatment changes from recurrence.

An increase in FLAIR signal of the fluid within the resection cavity might be a highly specific and early sign of local tumor recurrence/tumor progression also for brain metastases recurrence. 3).

Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, Johnson et al., sequenced the exomes of 23 initial low grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations in TP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis 4).

Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors.


1)
Calabrese C, Poppleton H, Kocak M, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11(1):69-82.
2)
Cheng L, Huang Z, Zhou W, et al. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013;153(1):139- 152.
3)
Bette S, Gempt J, Wiestler B, Huber T, Specht H, Meyer B, Zimmer C, Kirschke JS, Boeckh-Behrens T. Increase in FLAIR Signal of the Fluid Within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases? Rofo. 2017 Jan;189(1):63-70. doi: 10.1055/s-0042-119686. PubMed PMID: 28002859.
4)
Johnson BE, Mazor T, Hong C, Barnes M, Aihara K, McLean CY, Fouse SD, Yamamoto S, Ueda H, Tatsuno K, Asthana S, Jalbert LE, Nelson SJ, Bollen AW, Gustafson WC, Charron E, Weiss WA, Smirnov IV, Song JS, Olshen AB, Cha S, Zhao Y, Moore RA, Mungall AJ, Jones SJ, Hirst M, Marra MA, Saito N, Aburatani H, Mukasa A, Berger MS, Chang SM, Taylor BS, Costello JF. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science. 2014 Jan 10;343(6167):189-93. doi: 10.1126/science.1239947. Epub 2013 Dec 12. PubMed PMID: 24336570; PubMed Central PMCID: PMC3998672.
  • tumor_recurrence.txt
  • Last modified: 2018/10/13 19:16
  • by administrador