The General Hospital Corporation

Aalborg University

Naar, Anders M.

Rajurkar, Mihir Shivadatta

Shyamala Maheswaran

Daniel Arie Haber

David T Ting

David Tomoaki Miyamoto

Nicola Aceto

Xin Hong

Tanya Todorova

Anders M Naar

Sakari Kauppinen

Andreas Petri

Mark Kalinich

Francesca Bersani

Mihir Shivadatta Rajurkar

Mehmet Toner

Ravi Kapur

Zongli Zheng

Sarah Javaid

Tilak K Sundaresan

A John Iafrate

David Tsai Ting

Tanya Todorova Kwan

This disclosure relates to new assay methods for analysis of RNA, e.g., from circulating tumor cells (CTCs), tumor-specific exosomes, or tumor-specific cell-free RNA, in a subject's blood sample to determine an expression level of one or more lineage markers in the blood sample, wherein the expression level of a specific one or more lineage markers is predictive of progression-free survival and overall survival for a specific anti-cancer treatment regimen in that subject.

Digital analysis of blood samples to determine efficacy of cancer therapies for specific cancers

Methods for treating cancer, e.g., cancer of epithelial origin, by specifically targeting human satellite II (HSATII) using sequence specific agents such as oligonucleotides.

Targeting human satellite II (HSATII)

This disclosure relates to new assay methods for analysis of circulating tumor cells (CTCs) in blood samples for detection, e.g., early detection, and/or monitoring of disease, e.g., cancer. The methods provide ultra-high sensitivity and specificity, and include the use of microfluidic isolation of CTCs and digital detection of RNA derived from the CTCs.

Digital analysis of circulating tumor cells in blood samples

Described herein are methods and assays relating to the presence and/or level of circulating tumor cells (CTCs). These CTC-Cs represent a highly metastatic subpopulation of CTCs. In some embodiments, the methods and assays described herein relate to the treatment of cancer.

Methods relating to circulating tumor cell clusters and the treatment of cancer

Methods for diagnosing cancer based on detecting the presence of increased levels of expression of satellite repeats and/or Line-1.

Biomarkers of cancer

Provided herein are assays and methods related to determining a ratio of expression levels of PSA/PSMA or determining the expression level of PSMA in circulating tumor cells for diagnosis and/or for the purpose of monitoring treatment efficacy for prostate cancers that are likely hormone resistant.

Diagnosis and monitoring treatment of prostate cancer

The technology described herein relates to methods of detecting circulating tumor cells (CTCs), e.g. by detecting changes in the expression of certain CTC marker genes. Aberrant expression of CTC marker genes, e.g. changes in expression indicative of CTCs can also be targeted in order to treat cancer.

Methods and assays relating to circulating tumor cells

Ultra-sensitive assays for the detection of mutations, e.g., from blood-based sources of tumor genetic material (circulating tumor cells or plasma), or other settings in which limiting amounts of DNA, e.g., tumor DNA, is available. The assay is exemplified in the estrogen receptor, but is broadly customizable to target mutations in other genes.

LNA-based mutant enrichment next-generation sequencing assays

Methods for treating cancer, e.g., cancer of epithelial origin, by specifically targeting human satellite II (HSATII) using sequence specific agents such as oligonucleotides. As shown herein, the hetero chromatic HSATII satellite repeat is silenced in normal cells, but massively over expressed in epithelial cancers and in cancer cell lines when grown as xenografts or in 3D culture. Induction of HSATII RNA, either in xenografts or using in vitro reconstitution models, suggests the appearance of complementary DNA intermediates.

Methods of isolating, enriching, capturing, identifying, or detecting the presence of, cancerous cells in a sample, e.g., a blood sample from a subject, by detecting the presence of one or more cancer cell surface markers selected from the group consisting of cadherin 1 (CDH1), CDH2, CDH3, CDH4, CDH5, CDH9, CDH11, CDH17, CDH19, protocadherin 9 (PCDH9) and/or PCDH beta 13 (PCDHb13), and optionally an additional cancer cell surface marker, e.g., EpCAM, MUC1, EphB4, EGFR, CEA, and/or HER2.

Growing community of inventors

Lexington, MA, United States of America

Shyamala Maheswaran