52 results about "Antiangiogenic therapy" patented technology

Embodiments are related to the accurate detection of somatic mutations in the plasma (or other samples containing cell-free DNA) of cancer patients and for subjects being screened for cancer. The detection of these molecular markers would be useful for the screening, detection, monitoring, management, and prognostication of cancer patients. For example, a mutational load can be determined from the identified somatic mutations, and the mutational load can be used to screen for any or various types of cancers, where no prior knowledge about a tumor or possible cancer of the subject may be required. Embodiments can be useful for guiding the use of therapies (e.g. targeted therapy, immunotherapy, genome editing, surgery, chemotherapy, embolization therapy, anti-angiogenesis therapy) for cancers. Embodiments are also directed to identifying de novo mutations in a fetus by analyzing a maternal sample having cell-free DNA from the fetus.

Methods, compositions and kits are provided for assessing angiogenesis through sensitive, direct detection of activation of endothelial cells at molecular levels. In general, activation of endothelial cells is detected by measuring the levels of cellular components and their protein complexes participating in a specific angiogenesis signaling pathway in endothelial cells. The methods can be used for assessing status of diseases associated with undesirable angiogenesis, such as the likelihood of developing the disease, presence or absence of the disease, prognosis of the disease and the likelihood of response or resistance to a particular anti-angiogenic therapy. The methods can also be used to guide the design of effective therapeutic regimens targeting a specific angiogenic signaling pathway, as well as in conjunction with therapeutic intervention of diseases or conditions associated with undesirable angiogenesis.

To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.

The present invention relates to a method for monitoring subjects being on anti-angiogenesis therapy based on determining the amount of a cardiac troponin in a first and second sample of a subject and comparing the amount in the first sample with the second sample. Thereby, it can be assessed whether a subject is susceptible to a continuation of the therapy or not. Moreover, the present invention relates to a method for predicting the risk of a cardiovascular event as a consequence of anti-angiogenesis therapy. Also encompassed by the present invention are kits and devices adapted to carry out the method of the present invention.

The present invention provides methods for treating metastatic cancer comprising identifying subjects who will respond favorably to anti-VEGF therapy. According to certain aspects of the invention, subjects are identified based on their expression level of one or more predictive biomarkers. Favorable response to anti-VEGF therapy is indicated by high expression levels of certain biomarkers or by low expression levels of certain biomarkers. An exemplary predictive biomarker is VEGF-A. Also disclosed herein are prognostic biomarkers useful for identifying cancer-bearing subjects who are expected to have better relative survival outcomes.

The present invention provides methods and systems for the detection of tumor vessel response to antiangiogenic therapies. The present invention also provides compositions and methods for therapeutic and research applications. In particular, the present invention provides systems and methods that employ CD26, HIF-1, and HIF-1 pathway components as biomarkers for monitoring antiangiogenic therapies and as therapeutic targets.

Peptide motifs which define specificity of tumor-derived endothelial cells. These peptides possess a charge motif of positive-positive-hydrophobic which is important in determining the specificity of binding to tumor-derived endothelium. The specific molecular peptide motifs will facilitate diverse therapeutic and diagnostic applications including: anti-angiogenic therapies to be used in alone or in conjunction with standard therapies; imaging tools for both detection of very small metastasis that are undetectable by current techniques; for monitoring tumor response; for targeting and directing chemotherapy drugs to the tumor; for treatment of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, for treating some forms of blindness; as well as other diagnostic and therapeutic applications.

It has now been determined that α6β4 integrin is a pro-angiogenic receptor, and thus that it provides a novel and heretofore unrecognized target for anti-angiogenic therapy. Thus, angiogenesis, particularly pathological angiogenesis, can be inhibited, and conditions with which pathological angiogenesis is associated treated using inhibitors of α6β4 integrin. A tissue in which angiogenesis is to be inhibited is exposed to a therapeutic agent effective to reduce the amount of active α6β4 integrin in the tissue. The tissue may be within a patient, and in particular a human patient to be treated for a disease condition with which pathological angiogenesis is associated. The therapeutic agent may be an antibody or a small molecule, for example a laminin-5 analog, which binds to α6β4 integrin and inhibits its normal function. The therapeutic agent may also be a chemical species that interferes with the production of α6β4 integrin, including for example an antisense or RNAi species.

This invention describes the new 6-alkenyl- and 6-alkinyl-epothilone derivatives of general formula (I) in which R^1a, R^1b, R^2b, R^3a, R^3b, R⁴, R⁵, R⁶, R⁷, A, Y, D, E, G, Y and Z have the meanings that are indicated in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and thus find use in treating diseases or conditions associated with the need for cell growth, division and/or proliferation. Thus the compounds are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (such as psoriasis, arthritis). Methods of use and preparation of the compounds are also described.

The present invention is based on the identification of novel biomarkers predictive of responsiveness to a combination of anti-immune checkpoint and anti-angiogenesis therapies.

Disclosed are copper-binding compounds with improved properties and methods of using such compounds in the prevention and treatment of angiogenic diseases, such as cancer. Advantages of the invention include the enhanced stability of the compounds, which is achieved without reduction in efficacy. Pharmaceutical compositions, therapeutic kits and combination treatment methods and uses are also provided.