Compositions and methods for treating individuals who have oncogene-negative cancer

A composition formulated for use in a method of treating an individual who has an oncogene-negative cancer, wherein the composition comprises an inhibitor of Ras/MAPK pathway activity.

A kit for use in a method of treating an individual who has an oncogene-negative cancer, the kit comprising:

• (a) an inhibitor of Ras/MAPK pathway activity;
• and (b) an inhibitor of PI3K-AKT pathway activity, wherein the components of the kit are separated from one another.

A method for testing candidate therapies, the method comprising:

• (a) administering a candidate therapeutic agent to a non-human genetically modified mammal that has an oncogene-negative genomic profile and comprises lung cells with one or more genomic alterations causing increased Ras/MAPK pathway activity and/or increased PI3K-AKT pathway activity;
• and
• (b) determining whether the candidate therapeutic agent prevented or reduced lung cancer in the individual relative to a control.

A method for testing candidate therapies, the method comprising:

• (a) contacting a population of cells with a candidate therapeutic agent, wherein said cells are mammalian cells that have an oncogene-negative genomic profile and comprise one or more genomic alterations causing increased Ras/MAPK pathway activity and/or increased PI3K-AKT pathway activity;
• and
• (b) determining whether the candidate therapeutic agent prevented or reduced proliferation of said population of cells relative to a control.

An oncogene-negative mouse for use as a lung cancer model, comprising:

• an oncogene-negative genomic profile and genomic alterations causing increased Ras/MAPK pathway activity and increased PI3K-AKT pathway activity.