Over the past two decades, elucidation of the genetic defects that underlie cancer has
resulted in a plethora of novel targeted cancer drugs. Although these agents can initially be …

The first wave of genetically targeted therapies for cancer focused on drugging gene
products that are recurrently mutated in specific cancer types. However, mutational analysis …

INTRODUCTION Genetic interactions occur when mutations in two or more genes combine
to generate an unexpected phenotype. An extreme negative or synthetic lethal genetic …

A synthetic lethal interaction occurs between two genes when the perturbation of either gene
alone is viable but the perturbation of both genes simultaneously results in the loss of …

The Myc proto-oncogene family consists of three members, C-MYC, MYCN, and MYCL,
which encodes the transcription factor c-Myc (hereafter Myc), N-Myc, and L-Myc …

The genetic concept of synthetic lethality has now been validated clinically through the
demonstrated efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of …

Selective inhibitors of PARP1 and PARP2 (PARP1/2) are used to treat cancer patients with
deficiencies in the repair of DNA via homologous recombination. Here we provide a …

An underlying hallmark of cancers is their genomic instability, which is associated with a
greater propensity to accumulate DNA damage. Historical treatment of cancer by …

Mitochondria are essential for tumor growth and progression. However, the heavy demand
for mitochondrial activity in cancer leads to increased production of mitochondrial reactive …

Synthetic lethality (SL) provides a conceptual framework for tackling targets that are not
classically “druggable,” including loss-of-function mutations in tumor suppressor genes …