Novel chemical entities affecting neuroblastoma tumor-initiating cells

Abstract

Disclosed are neuroblastoma tumor-initiating cell inhibiting compositions comprising chemical entities capable of affecting neuroblastoma tumor-initiating cells. Pharmaceutical preparations that include these chemical entities are also provided for the treatment of neuroblastoma. These pharmaceutical preparations are suitable for the treatment of humans, and are particularly suited for the treatment of children of 12 years of age or younger having neuroblastoma. The compositions and pharmaceutical preparations posses reduced normal cell cytotoxicity. The compositions and pharmaceutical preparations may be used alone or together with other conventional neuroblastoma preparations as part of a clinical regimen in the treatment and management of neuroblastoma.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application makes reference to the following co-pending U.S. patent application. The application is U.S. App. No. 60 / 739,337, entitled “Cancer Stem Cells and Uses Thereof,” filed Nov. 23, 2005. The entire disclosure and contents of the above application is hereby incorporated by reference.BACKGROUND [0002] 1. Field of the Invention [0003] The present invention relates to the field of pharmacologically active chemical compositions useful in affecting neuroblastoma tumor-initiating cells, and the use of such compositions in the treatment of neuroblastoma and related conditions. [0004] 2. Related Art [0005] Neuroblastoma (NB) is the most common extracranial solid tumor in children, with poor survival rates in children with metastatic disease. NB is estimated to be responsible for about 15% of cancer-related deaths in children (1,2). The survival rate for metastatic NB is estimated to be less than 30%. In the majority of these cases, c...

AI Technical Summary

Benefits of technology

[0060] In some embodiments, the chemical entities of the invention may be described as compounds that possess specific cytostatic or cytotoxic activity toward neuroblastoma tumor-initiating cells. In other embodiments, the neuroblastoma-inhibiting composition further comprises ancitabine hydrochloride, doxorubicin hydrochloride, etoposide, vincristine sulfate, or a combination thereof. In yet other embodiments, the neuroblastoma inhibiting composition may be further described as having reduced non-neuroblastoma tumor-initiating cell cytotoxicity.

[0105] In yet other embodiments, the neuroblastoma tumor-inhibiting cells are in an animal having neuroblastoma. In some embodiments, the animal is a human. In some embodiments, the human is 12 years of age or younger. That is, it is anticipated that the invention is particularly useful in the treatment of children afflicted with neuroblastoma, and will have a profound effect on reducing the high rate of mortality in this population of neuroblastoma patients.

[0106] The method may be further described as administering a composition that has a reduced non-neuroblastoma tumor-initiating cell cytotoxicity. It is expected that the methods and compositions of the present invention will provide fewer and / or less pronounce undesirable side affect in the treatment of a patient as a result. In some embodiments, the composition employed in the method is essentially free of non-neuroblastoma tumor cell inhibiting activity.

Problems solved by technology

Neuroblastoma (NB) is the most common extracranial solid tumor in children, with poor survival rates in children with metastatic disease.

In the majority of these cases, conventional cancer therapies have been ineffective.

Unfortunately, genetic mutations that contribute to the origin and progression of 98% of NB cases have not been identified.

In contrast, NB tumors in children over one-year-old often grow aggressively, disseminate to the bone and bone marrow, and are fatal in the vast majority of cases.

For example, many current therapies kill the bulk of proliferating tumor cells, but these cells may not be intrinsically tumorigenic, and in many cases the TICs may escape the effects of the therapeutic agents, leading to tumor relapse.

However, a tumor initiating cell population from tumor tissue in a patient with neuroblastoma has not been isolated.

However, a population of tumor initiating cells from such solid tumor tissue has not yet been reported.

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