Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy.

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Jenner ZB, Sood AK, Coleman RL

Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy.

Future Oncol. 2016 Jun;12(12):1439-56. doi: 10.2217/fon-2016-0002. Epub 2016 Apr 18.

PubMed ID

27087632 [ View in PubMed

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Abstract

Rucaparib camsylate (CO-338; 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd ]indol-6-one ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt) is a PARP1, 2 and 3 inhibitor. Phase I studies identified a recommended Phase II dose of 600 mg orally twice daily. ARIEL2 Part 1 established a tumor genomic profiling test for homologous recombination loss of heterozygosity quantification using a next-generation sequencing companion diagnostic (CDx). Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy. Comparable to rucaparib development, other PARP inhibitors, such as olaparib, niraparib, veliparib and talazoparib, are developing CDx tests for targeted therapy. PARP inhibitor clinical trials and CDx assays are discussed in this review, as are potential PARP inhibitor combination therapies and likely resistance mechanisms.

DrugBank Data that Cites this Article

Drugs

Rucaparib

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Rucaparib	Poly [ADP-ribose] polymerase 1	Protein	Humans	Yes	Inhibitor	Details
Rucaparib	Poly [ADP-ribose] polymerase 2	Protein	Humans	Yes	Inhibitor	Details
Rucaparib	Poly [ADP-ribose] polymerase 3	Protein	Humans	Yes	Inhibitor	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Rucaparib	Solute carrier family 22 member 1	Protein	Humans	No	Inhibitor	Details