University of California

Cephalon, Inc.

Other

Lorenzo M Leoni

Dennis A Carson

Howard B Cottam

Maripat Corr

Chae-Seo Rhee

Malini Sen

Soichi Adachi

Christina Wu

Souchi Adachi

Mary Patricia Corr

Hsien C Shih

The diverse receptor-ligand pairs of the Wnt and frizzled (Fzd) families play important roles during embryonic development, and thus may be overexpressed in cancers that arise from immature cells. The mRNA levels and expression levels of 5 Wnt (Wnt-1, 5a, 7a, 10b, 13) and 2 Fzd (Fzd-2, 5) genes in 10 head and neck squamous carcinoma cell lines (HNSCC) were investigated. In addition, anti-Wnt-1 antibodies were used to study the Wnt/Fzd signalling pathway. These results indicate that HNSCC cell lines overexpress one or more Wnt and Fzd genes, and the proliferation and survival of a subset of HNSCC may depend on the Wnt/Fzd pathway. Therefore, the Wnt and Fzd receptors may be useful targets for immunotherapy of this common cancer.

Wnt and frizzled receptors as targets for immunotherapy in head and neck squamous cell carcinomas

The diverse receptor-ligand pairs of the Wnt and frizzled (Fzd) families play important roles during embryonic development, and thus may be overexpressed in cancers that arise from immature cells. The mRNA levels and expression levels of 5 Wnt (Wnt-1, 5a, 7a, 10b, 13) and 2 Fzd (Fzd-2, 5) genes in 10 head and neck squamous carcinoma cell lines (HNSCC) were investigated. In addition, anti-Wnt-1 antibodies were used to study the Wnt/Fzd signalling pathway. These results indicate that HNSCC cell lines overexpress one or more Wnt and Fzd genes, and the growth and survival of a subset of HNSCC may depend on the Wnt/Fzd pathway. Therefore, The Wnt and Fzd receptors may be useful targets for immunotherapy of this common cancer.

The present invention provides novel indole derivatives useful to inhibit cancer or sensitize cancer cells to chemotherapeutic agents, radiation or other anti-cancer treatments.

Indole compounds useful for the treatment of cancer

The present invention provides a therapeutic method to treat non-malignant diseases characterized by the excessive tissue growth, e.g., hyperplastic diseases, comprising administering to a mammal (e.g., human) afflicted with excessive tissue growth, an effective amount of a derivative of an indole compound of formula (I):formula (I):wherein Ris lower alkyl, (hydroxy)lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, phenyl, benzyl or 2-thienyl; R, R, Rand Rare the same or different and are each hydrogen or lower alkyl; each Ris individually hydrogen, lower alkyl, hydroxy, (hydroxy)lower alkyl, lower alkoxy, benzyloxy, lower alkanoyloxy, nitro or halo, Ris hydrogen, lower alkyl or lower alkenyl, X is oxy and thio, Y is carbonyl, &#x2014;(CH)&#x2014;, &#x2014;(C-C)alkyl(CO)&#x2014;, or &#x2014;(CH)SO&#x2014;; Z is hydroxy, lower alkoxy, (C-C)acyloxy, &#x2014;N(R)(R), phenylamino, (&#x3c9;-(4-pyridyl)(C-Calkoxy), (&#x3c9;-((R)(R)amino)(C-Calkoxy), an amino acid ester of (&#x3c9;-(HO)(C-C))alkoxy, &#x2014;N(R)CH(R)COH, 1'-D-glucuronyloxy, &#x2014;SOH, &#x2014;POH, &#x2014;N(NO)(OH), &#x2014;SONH, &#x2014;PO(OH)(NH), &#x2014;OCHCHN(CH), or tetrazolyl; wherein Rand Rare each H, (C-C)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R), S or nonperoxide O; n is 0, 1, 2, or 3; wherein Rand Rare each H, (C-C)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R), S or nonperoxide O; each alkyl or phenyl group of R, R, R, R, R, R, Rand Z is optionally substituted with 1, 2, or 3 (C-C)alkyl groups; or a pharmaceutically acceptable salt thereof.

Use of etodolac to treat hyperplasia

A method of treating cancer is provided comprising administering an amount of etodolac or analog theteof to a subject afflicted with leukemia that is effective to reduce the viability and/or to sensitize leukemia cells to an anti-cancer agent.

Use of etodolac for the treatment of chronic lymphocytic leukemia

Compositions and methods involving agents that specifically bind to methylthioadenosine phosphorylase (MTAP) protein are disclosed. Illustrative compositions comprise binding agents that bind to human MTAP protein in biological samples, including embedded samples. The binding agents are useful, for example, in the detection, prognosis, and/or treatment of MTAP deficient cancers. Also disclosed are kits containing the reagents necessary for the detection of human MTAP protein in an embedded sample.

Compositions and methods for the detection and treatment of methylthioadenosine phosphorylase deficient cancers

A method of treating cancer is provided comprising administering an amount of etodolac to a subject afflicted with cancer that is effective to reduce the viability and/or to sensitize the cancer to an anti-cancer agent.

Use of etodolac for the treatment of prostate cancer

A method of treating multiple myeloma (MM) is provided comprising administering an amount of etodolac to a subject afflicted with MM that is effective to selectively reduce the viability of and/or to sensitize the cancer cells to an anti-cancer agent.

Use of etodolac in the treatment of multiple myeloma

The present invention provides compounds that act to suppress p53 activity in mammalian cells, and a method to effectively suppress p53 activity in the cells of a mammal subject to a stress or pathology that is ameliorated by such suppression.

Inhibition of p53-induced stress response

A new family of inadone and tetralone tubulin-binding compounds (TBs) is disclosed. Unlike classical TBs, which inhibit mitosis among affected dividing cells, the TBs of the invention possess two unique properties: (1) they induce apoptosis among stationary phase (non-dividing) malignant cells, yet do not impair the viability of normal nonproliferating cells; and, (2) they affect cells which have acquired MDR more powerfully than they affect cells without MDR. Thus, the TBs of the invention provide means to target malignant cells for chemotherapy, even after previous therapies have failed, without affecting normal cells and tissues in the host.

Growing community of inventors

San Diego, CA, United States of America

Lorenzo M Leoni