This disclosure relates to methods of and compositions for reducing expression or activity of a variant gene comprising at least one mutation as compared its wild-type gene, comprising introducing into a cell comprising the variant gene one or more DNA sequences encoding two or more gRNAs that are complementary to two or more target sequences in the variant gene, wherein at least one of the gRNAs hybridizes to a target sequence comprising a PAM site in the variant gene that results from a mutation to the variant gene creating the PAM site that does not exist in the wild-type gene or is operably linked to a mutated portion of the wild-type gene, at least one of the gRNAs hybridizes to a target sequence comprising a PAM site in an intron of the variant gene downstream or upstream from the PAM site, and a nucleic acid sequence encoding a CRISPR-associated endonuclease; wherein a CRISPR-associated endonuclease cleaves the variant gene at the target sequences; and expression or activity of the variant gene is reduced in the cell relative to a cell in which the one or more DNA sequences encoding the two or more gRNAs and the nucleic acid sequence encoding the CRISPR-associated endonuclease are not introduced.

The invention provides a complex comprising Zn2+ and a compound of formula (I): or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt thereof that is useful for treating cancer, as well as compositions and kits comprising such complexes.

##STR00001##

Described herein are methods of treating PIK3CA-mutant cancer patients by administering metformin and a PI3K alpha inhibitor.

Provided are combinations of poziotinib and an anti-HER1, anti-HER2 or anti-HER4 antibody, optionally with other agents, and use of the combinations for treating cancer.

The present invention relates to an orally disintegrating pharmaceutical composition comprising Nefopam and pharmaceutically acceptable inert excipients and a process or preparing the same. The composition comprises 5 to 10% w/w of Nefopam with respect to weight of the composition

The present disclosure provides, inter alia, nanoparticle formulations comprising nanoparticles of a polymer loaded with a system x.sub.c.sup.− inhibitor, such as a nanoparticle formulation comprising nanoparticles of PEG-PLGA loaded with IKE or a pharmaceutically acceptable salt thereof. Methods of preparing such nanoparticle formulations, methods of treating cancers in a subject or selectively killing cancer cells using such nanoparticle formulations, and kits comprising such nanoparticle formulations are also provided.

Dosage forms containing nefopam, nefopam metabolite, nefopam prodrug, isomers thereof or combinations of the foregoing, optionally an acid, and optionally an opioid analgesic and/or NSAID, and associated methods for treating various types of pain in patients.

Dosage forms containing nefopam, nefopam metabolite, nefopam prodrug, isomers thereof or combinations of the foregoing, optionally an acid, and optionally an opioid analgesic and/or NSAID, and associated methods for treating various types of pain in patients.

Dosage forms containing nefopam, nefopam metabolite, nefopam prodrug, isomers thereof or combinations of the foregoing, optionally an acid, and optionally an opioid analgesic and/or NSAID, and associated methods for treating various types of pain in patients.

Dosage forms containing nefopam, nefopam metabolite, nefopam prodrug, isomers thereof or combinations of the foregoing, optionally an acid, and optionally an opioid analgesic and/or NSAID, and associated methods for treating various types of pain in patients.