Sunday, November 24, 2019

Very Brief Blog: Some Cancers May Be Driven by Extrachromasomal DNA; Potential Drug Target

Over the past year or two, there's been a boom of interest in non-chromosomal oncogenes and the role they may play in some tumors.  For a number of years, we've known that tumors can be a rapidly evolution genetic mess, with missing chromosomes, extra copy numbers of oncogenes, fusions, and other alterations.

UCSD medical scientist Paul Mischel and team made a splash with a November 20 publication in Nature, documenting more about these tiny circular extrachromosomal elements (ecDNA), as well as showing they can over-express the oncogenes of interest, just like a fusion-driven oncogene that is "always on." 

Because normal tissues aren't driven by ecDNA, future drugs that eliminate ecDNA might be a magic bullet against some of the cancers, or at least, powerful assets in multi-drug regimens.

Some entry points:
  • UCSD's Paul Mischel MD at Wikipedia here.
  • Mischel lab at UCSD's Ludwig Cancer Center here.
  • Mischel lab website here.
  • Nature new paper here:   Wu et al. (2019) Circular ecDNA promotes accessible chromatin and high oncogene expression.  Nature (epub 20 November).
  • Nature Reviews Cancer paper here:  Verhaak, Bafna, Mischel (2019)  Extrachrosomal oncogene amplification in tumour pathogenesis and evolution.  Nat Rev Cancer 19:283-8.
  • Trade Press:
    • Live Science here.
    • Fierce Biotech here.
  • New York Times - November 20 - here.
  • Website for start-up biotech company, Boundless Bio, here.
    • Raises $46M, September 2019, here.
    • Mischel listed as founder; Zachary Hornby as CEO (Linked In here).
Verhaak, Nat Rev Cancer, Fig 01.  Bottom, EM of microcircular ecDNA.

Mischel and I were just a couple years apart in the pathology residence and neuropathology fellowship at UCLA (circa 1994). MIschel's background includes college at Penn, med school at Cornell, residency at UCLA, molecular biology fellowship at UCSF, and faculty positions at UCLA and currently UCSD.