Described herein is a previously unknown function of XBP1 in triple-negative breast cancer (TNBC). It is shown that XBP1 is preferentially spliced and activated in TNBC, and that deletion of XBP1 significantly blocks triple negative breast tumor growth. Strikingly, XBP1 is required for the self-renewal of breast tumor initiating cells (TICs). Genome-wide mapping of the XBP1 transcriptional regulatory network identified a fundamental role for XBP1 in regulating the response to hypoxia via the transcription factor hypoxia-inducible factor 1.alpha. (HIF1.alpha.). Importantly, activation of this pathway appears to carry prognostic implications, as expression of the XBP1-dependent signature is associated with shorter survival times in human TNBC.

Cornell University

Modulation of breast cancer growth by modulation of XBP1 activity

Described herein is a method of treatment of cancer or tumor using a modified bacteria or composition comprising the modified bacteria. In certain embodiments, the method is in combination with other treatment. In certain embodiments, the treatment is chemotherapy, radiation therapy, gene therapy, surgery or a combination thereof. The method makes modified facultative anaerobic bacteria into a conditional obligate anaerobe. The modified bacteria are strictly hypoxia regulated and comprise an essential gene expressing cassette. The vectors of this method comprise the essential gene expressing cassette. Also described herein are therapeutic and prophylactic compositions comprising the modified bacteria. The therapeutic and prophylactic compositions contain a purified form of the modified bacteria, while in certain embodiments, they do not contain other strain of microorganisms. The modified bacteria grow within the solid tumor/cancer, retarding its growth and are rapidly eliminated from normal tissues. The solid tumor/cancer includes breast cancer, liver cancer or neuroblastoma.

The University of Hong Kong

Modified bacteria and their uses thereof for the treatment of cancer or tumor

There is provided a method for determining tumour metastatic potential using biomarkers of tumour metastasis comprising any two of carbonic anhydrase-9 (CAIX), vascular endothelial growth factor C (VEGF-C), ephrin A5 (EFNA5), eph receptor B2 (EPHB2), transforming growth factor beta 3 (TGF-.beta.3), pyruvate dehydrogenase kinase isoenzyme-3 (PDK3), carbonic anhydrase-12 (CAXII), keratin 14 (KRT14), hypoxia inducible factor 1 alpha subunit (HIF-1.alpha.), and tenascin C (TNC). CAIX, VEGF-C, EFNA5, EPHB2, TGF-.beta.3 or PDK3 may be indicators of moderate metastatic potential, while CAXII, KRT14, HIF-1.alpha., or TNC may be indicators of high metastatic potential. The biomarkers may be used to assess malignancies or cancers having hypoxic regions, such as breast cancer.

Lou; Yuanmei

McDonald; Paul Christopher

Oloumi; Arusha

Dedhar; Shoukat

British Columbia Cancer Agency Branch

Biomarkers of cancer metastasis

The present invention relates to a compound inhibiting HF-1 activity, a preparation method of the same, and a pharmaceutical composition comprising the same as an active ingredient. The compound of the present invention demonstrates anticancer activity not by non-selective cytotoxicity but by inhibiting the activity of HIF-1, the transcription factor playing an important role in cancer cell growth and metastasis. Accordingly, the compound or the pharmaceutically acceptable salt thereof according to the present invention inhibits HIF-1 activity, and therefore can be used as a therapeutic agent for solid tumors such as colon cancer, liver cancer, stomach cancer and breast cancer. In addition, the compound or the pharmaceutically acceptable salt thereof according to the present invention can be used as an active ingredient for a therapeutic agent for diabetic retinopathy or arthritis which may become worse when hypoxia-induced VEGF expression by HIF-1 increases.

Lee; Kyeong

Won; Mi Sun

Kim; Hwan Mook

Park; Song Kyu

Lee; Kiho

Lee; Ki Hoon

Lee; Chang Woo

Lee; Jung Joon

Chung; Kyung Sook

Kim; Bo Kyung

Jin; Yinglan

Lee; Seung-hee

Korea Research Institute of Bioscience and Biotechnology

Dongguk University Industry-Academic Cooperation Foundation

Aryloxy phenoxy acrylic compound having HIF-1 inhibition activity, method for preparing same, and pharmaceutical composition containing same as an active ingredient