Compositions and methods for modulating transcriptional activity of amplified oncogenes contained on extrachromosomal dna
AssigneesThe Regents of the University of California, Ludwig Institute for Cancer Research, The Board of Trustees of the Leland Stanford Junior University
InventorsPaul Mischel, Bing Ren, Kristen Turner, Sihan Wu, Vineet Bafna, Nam-phuong Nguyen, Howard Chang
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Abstract
Provided herein are, inter alia, methods and compositions to detect, monitor and treat cancer, wherein the cancer includes amplified extrachromosomal oncogenes. The methods are useful for personalized treatment and exploit differential expression and chromatin structure of extrachromosomal oncogenes in cancer cells.
Claims74
A method of treating cancer in a subject in need thereof, wherein the cancer comprises an oncogene contained on a circular extrachromosomal DNA, comprising:
- administering a transcriptional inhibitor of a gene contained on the circular extrachromosomal DNA, wherein the transcriptional inhibitor of the gene inhibits expression of the oncogene contained in circular extrachromosomal DNA.
A method of treating cancer in a subject in need thereof, wherein the cancer comprises an oncogene contained on a circular extrachromosomal DNA, comprising:
- administering a transcriptional inhibitor of a first gene contained on the circular extrachromosomal DNA, wherein the transcriptional inhibitor of the first gene inhibits expression of the first gene and the oncogene contained in circular extrachromosomal DNA.
A method of treating cancer in a subject in need thereof, wherein the cancer comprises an oncogene on a circular extrachromosomal DNA, comprising administering a therapeutically effective amount of an agent that decreases chromatin accessibility of the circular extrachromosomal DNA, thereby treating the cancer in the subject.
A method of treating cancer in a subject in need thereof, wherein cancer cells in the subject comprise a first extrachromosomal oncogene forming part of a circular extrachromosomal DNA, the method comprising administering to said subject a therapeutically effective amount of a transcriptional inhibitor of a first gene forming part of the circular extrachromosomal DNA in the cancer cells of the subject, wherein the first gene and the first extrachromosomal oncogene do or do not form part of a same topologically associating domain (TAD).
The method of claim 43, wherein said transcriptional inhibitors are independently different. 45 . The method of any one of claims 32-44, further comprising determining whether said first extrachromosomal oncogene is contained on circular extrachromosomal DNA.
A method of inhibiting expression of a gene in a subject, wherein the gene is contained on circular extrachromosomal DNA, comprising:
- administering a transcriptional inhibitor of the gene to the subject, thereby inhibiting the expression of the gene.
A method of inhibiting expression of a first gene and a second gene in a subject, wherein the first gene and second gene are contained on circular extrachromosomal DNA, comprising:
- administering a transcriptional inhibitor of the first gene to the subject, thereby inhibiting the expression of the first gene and the second gene.
Dependencies are inferred from the claim text.