Iniparib, a PARP1 inhibitor for the potential treatment of cancer, including triple-negative breast cancer.
Summary of "Iniparib, a PARP1 inhibitor for the potential treatment of cancer, including triple-negative breast cancer."
PARP inhibitors are a promising, novel class of anticancer agents. Iniparib (BSI-201) is an intravenously administered PARP1 inhibitor under development by BiPar Sciences Inc, a subsidiary of sanofi-aventis, under license from Octamer Inc, for the potential treatment of cancer. Iniparib, either alone or in combination with chemotherapy, had significant antitumor activity in preclinical studies in vitro and in vivo. Phase I clinical trials in patients with solid tumors demonstrated that treatment with iniparib was associated with minimal toxicity. Encouraging results were observed in a randomized phase II clinical trial, which demonstrated that the addition of iniparib to gemcitabine and carboplatin led to an improvement in clinical benefit rate, progression-free survival and overall survival in patients with metastatic triple-negative breast cancer (TNBC) compared with gemcitabine and carboplatin alone. A phase III clinical trial to test the survival benefit of iniparib in combination with gemcitabine and carboplatin in metastatic TNBC has completed accrual. Another phase III clinical trial will evaluate the overall survival of patients with newly diagnosed stage IV squamous NSCLC treated with gemcitabine and carboplatin with or without iniparib. Several phase II clinical trials of iniparib as a single agent or in combination with chemotherapy are ongoing in other tumor types, such as ovarian and uterine cancer, NSCLC and glioblastoma. These trials will clarify the role of iniparib in the treatment of cancer, including TNBC.
Affiliation
The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA. tanan@umdnj.edu.
Journal Details
This article was published in the following journal.
Name: IDrugs : the investigational drugs journal
ISSN: 2040-3410
Pages: 646-56
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20799148
- DOI: http://dx.doi.org/
Medical and Biotech [MESH] Definitions
Fadrozole
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.
Megestrol
17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer.
Hemibody Irradiation
Irradiation of one half or both halves of the body in the treatment of disseminated cancer or widespread metastases. It is used to treat diffuse metastases in one session as opposed to multiple fields over an extended period. The more frequent treatment modalities are upper hemibody irradiation (UHBI) or lower hemibody irradiation (LHBI). Less common is mid-body irradiation (MBI). In the treatment of both halves of the body sequentially, hemibody irradiation permits radiotherapy of the whole body with larger doses of radiation than could be accomplished with WHOLE-BODY IRRADIATION. It is sometimes called "systemic" hemibody irradiation with reference to its use in widespread cancer or metastases. (P. Rubin et al. Cancer, Vol 55, p2210, 1985)
American Cancer Society
A voluntary organization concerned with the prevention and treatment of cancer through education and research.
Aminoglutethimide
An aromatase inhibitor that produces a state of "medical" adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454)
PubMed Articles
Iniparib in metastatic triple-negative breast cancer.
Iniparib plus chemotherapy in metastatic triple-negative breast cancer.
Triple-negative breast cancers have inherent defects in DNA repair, making this cancer a rational target for therapy based on poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition.
Re: Potential Pitfalls of Crossover and Thoughts on Iniparib in Triple-Negative Breast Cancer.
Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta-analysis.
Although poly(ADP-ribose) polymerase-1 (PARP1) inhibition is a recent promising therapy in breast cancer, PARP1 expression in this disease is not known. Using DNA microarray and array-based comparativ...
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Prior studies have demonstrated that inhibition of CHK1 can promote activation of ERK1/2 and phosphorylation of histone H2AX, and also that inhibition of PARP1 can impact on growth factor-induced ERK1...
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