Poly(ADP-ribose) polymerase inhibitors in triple-negative breast cancer Journal Article
| Authors: | Comen, E. A.; Robson, M. |
| Article Title: | Poly(ADP-ribose) polymerase inhibitors in triple-negative breast cancer |
| Abstract: | Poly(ADP-ribose) polymerases (PARPs) are involved in many aspects of the cellular response to various forms of damage. PARP-1 and PARP-2, the most abundant PARPs, are central to the response to specific types of DNA damage, especially single-strand breaks. Inhibition of PARP activity may sensitize the cell to exogenous agents such as chemotherapy and radiation. In circumstances where rescue pathways are deficient, particularly the homologous recombination (HR)-directed DNA repair pathway, inhibition of PARP may result in "synthetic lethality." BRCA mutation-associated breast cancers are a paradigm of HR-directed repair deficient tumors. Early clinical trials have demonstrated significant activity of single-agent PARP inhibitors in BRCA-deficient breast and ovarian cancer. Because of phenotypic similarities between some "triple-negative" breast cancers (TNBC) and the most prevalent type of breast cancer seen in BRCA1 mutation carriers, some have hypothesized that TNBC might also be specifically sensitive to PARP inhibition. The activity of single-agent PARP inhibitors in TNBC has not been reported. One trial did suggest significant enhancement of the activity of platinum-based combination chemotherapy, without incremental toxicity. These studies indicate that PARP inhibition is an exciting new approach to the treatment of breast cancers in women with underlying BRCA mutations and possibly in sporadic cancers with defects in HR-directed repair. Future studies will be necessary to determine whether the effectiveness of PARP inhibitors in nonhereditary cancer requires an underlying HR defect or whether these agents may improve the activity of conventional chemotherapy by other means. In addition, studies will be required to determine whether PARP inhibitors may induce synthetic lethality in tumors with defects in pathways other than the BRCA-dependent DNA repair pathway. If either or both of these prove to be the case, then PARP inhibition may benefit a wide spectrum of cancer patients. © 2010 Lippincott Williams & Wilkins, Inc. |
| Keywords: | cancer chemotherapy; unclassified drug; gene mutation; clinical trial; fatigue; review; cisplatin; doxorubicin; cancer combination chemotherapy; monotherapy; nonhuman; gemcitabine; paclitaxel; adjuvant therapy; topotecan; antineoplastic agent; protein function; colorectal cancer; dna damage; dna repair; carboplatin; melanoma; enzyme inhibition; multiple cycle treatment; ovary cancer; breast cancer; gastrointestinal symptom; nausea; thrombocytopenia; gene function; cyclophosphamide; antineoplastic activity; enzyme activity; breast neoplasms; brca1 protein; brca2 protein; prostate cancer; sarcoma; enzyme inhibitors; enzyme inactivation; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; receptor, erbb-2; receptors, estrogen; receptors, progesterone; platinum derivative; drug cytotoxicity; taxane derivative; somnolence; anthracycline derivative; absence of side effects; brca1; brca2; cancer cell destruction; radiosensitization; mood disorder; bsi 201; olaparib; single stranded dna break; drug indication; poly(adp-ribose) polymerases; basal-like; base excision repair; homologous recombination-directed repair; poly(adp-ribose) polymerase (parp); synthetic lethality; 2 (2 methyl 2 pyrrolidinyl) 1h benzimidazole 4 carboxamide; 8 fluoro 3,4 dihydro 2 [4 (methylaminomethyl)phenyl]pyrrolo[3,4,5 e,f][2]benzazepin 6(5h) one; ino 1001; methylnitrosourea; mk 4827; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 2; chemosensitization; triple negative breast cancer |
| Journal Title: | The Cancer Journal |
| Volume: | 16 |
| Issue: | 1 |
| ISSN: | 1528-9117 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2010-01-01 |
| Start Page: | 48 |
| End Page: | 52 |
| Language: | English |
| DOI: | 10.1097/PPO.0b013e3181cf01eb |
| PUBMED: | 20164690 |
| PROVIDER: | scopus |
| PMCID: | PMC4035043 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 20 April 2011" - "CODEN: CAJOC" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work