BNP7787-mediated modulation of paclitaxel- and cisplatin-induced aberrant microtubule protein polymerization in vitro

Aulma R. Parker, Pavankumar N. Petluru, Meizhen Wu, Min Zhao, Harry Kochat, Frederick H. Hausheer

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Taxane and platinum drugs are important agents in the treatment of cancer and have shown activity against a variety of tumors, including ovarian, breast, and lung cancer, either as single agents or in combination with other chemotherapy drugs. However, a serious and prevalent side effect of taxane (docetaxel and all formulations/derivatives of paclitaxel) and platinum (cisplatin, carboplatin, and oxaliplatin) agents is dose-limiting chemotherapy-induced peripheral neuropathy (CIPN). CIPN can result in treatment delays, dose modifications, and, in severe cases, discontinuation of chemotherapy. Consequently, effective treatments for CIPN are needed. Dimesna (BNP7787; Tavocept ™; disodium 2,2′-dithio-bis-ethanesulfonate) is an investigational drug that is undergoing international clinical development as a treatment that is coadministered with first-line taxane and platinum combination chemotherapy in patients with inoperable advanced primary adenocarcinoma of the lung. BNP7787 is currently being developed with the objective of increasing the survival of cancer patients receiving taxane- and/or cisplatin-based chemotherapy. Additional data indicate that BNP7787 may also protect against common and serious chemotherapy-induced toxicities, including chemotherapy-induced anemia, nausea, emesis, nephrotoxicity, and neuropathy, without interfering with antitumor activity of the chemotherapeutic agent(s). Studies herein show that BNP7787 prevents aberrant microtubule protein (MTP) polymerization that is caused by exposure of MTP to paclitaxel or cisplatin. BNP7787 modulates paclitaxel-induced hyperpolymerization of MTP in a dose-dependent manner, and mesna, an in vivo metabolite of BNP7787, protects against time-dependent cisplatin-induced inactivation of MTP. We propose that interactions between BNP7787 and MTP may play a role in BNP7787-mediated protection against CIPN.

Original languageEnglish (US)
Pages (from-to)2558-2567
Number of pages10
JournalMolecular Cancer Therapeutics
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2010

Fingerprint

Microtubule Proteins
Polymerization
Drug Therapy
Peripheral Nervous System Diseases
Platinum
oxaliplatin
docetaxel
Cisplatin
2,2'-dithiodiethanesulfonic acid
In Vitro Techniques
TP protocol
Mesna
Investigational Drugs
Neoplasms
Carboplatin
Therapeutics
Paclitaxel
Combination Drug Therapy
Pharmaceutical Preparations
Ovarian Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

BNP7787-mediated modulation of paclitaxel- and cisplatin-induced aberrant microtubule protein polymerization in vitro. / Parker, Aulma R.; Petluru, Pavankumar N.; Wu, Meizhen; Zhao, Min; Kochat, Harry; Hausheer, Frederick H.

In: Molecular Cancer Therapeutics, Vol. 9, No. 9, 01.09.2010, p. 2558-2567.

Research output: Contribution to journalArticle

Parker, Aulma R. ; Petluru, Pavankumar N. ; Wu, Meizhen ; Zhao, Min ; Kochat, Harry ; Hausheer, Frederick H. / BNP7787-mediated modulation of paclitaxel- and cisplatin-induced aberrant microtubule protein polymerization in vitro. In: Molecular Cancer Therapeutics. 2010 ; Vol. 9, No. 9. pp. 2558-2567.
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AU - Hausheer, Frederick H.

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