University of Illinois

Jessie Peh

Paul Joseph Hergenrother

Steven C Zimmerman

Matthew W Boudreau

Chun-Ho Wong

Compositions and methods for the induction of cancer cell death. The compositions and methods include use of compositions in therapy for the treatment of cancer and for the selective induction of apoptosis in cancer cells. The drug combinations described herein can be synergistic and can have lower neurotoxicity effects than the same amounts of other compounds and combinations of compounds and can be effective when a particular cancer has become resistant to previously administered therapies.

PAC-1 combination therapy

The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Herein is demonstrated a strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner superior to combinations with MEK inhibitors. These data suggest the generality of drug-mediated MEK kinase cleavage as a therapeutic strategy to prevent resistance to targeted anticancer therapies.

Cancer therapy by degrading dual MEK signaling

Compositions and methods for the induction of cancer cell death. The compositions and methods of using them include use of compositions in therapy for the treatment of cancer and for the selective induction of apoptosis in cancer cells. The drug combinations described herein can be synergistic and can have lower neurotoxicity effects than the same amounts of other compounds and combinations of compounds and can be effective when a particular cancer has become resistant to previously administered therapies.

The invention provides compositions and methods for the induction of cancer cell death. The compositions and methods of using them include use of compositions in therapy for the treatment of cancer and for the selective induction of apoptosis in cancer cells. The drug combinations described herein can be synergistic and can have lower neurotoxicity effects than the same amounts of other compounds and combinations of compounds, and can be effective when a particular cancer has become resistant to previously administered therapies.

The invention provides compounds, compositions and methods for treating myotonic dystrophy. The compounds can selectively bind to CUG repeats in RNA, or to CTG repeats in DNA, and inhibit replication of the nucleic acids.

Growing community of inventors

Urbana, IL, United States of America

Jessie Peh