Macau University of Science and Technology

Xiao Jun Yao

Liang Liu

Lai Han Elaine Leung

Lai Han Leung

Ying Li

Lian Xiang Luo

Qian Qian Wang

Jia Hui Xu

Xing Xing Fan

Chun Xie

Elaine Lai-Han Leung

Lian-Xiang Luo

Vincent Kam-Wai Wong

David Ward

Hu Dan Pan

Yan Ling Zhou

A method of identifying a gene associated with a disease or pathological condition of the disease includes: a) obtaining a first group of exome sequences from a first population suffering from the disease or pathological condition and a second group of exome sequences from a second population not having the disease or pathological condition; b) identifying one or more variants in the first group by comparing it with the second group, and optionally with a public database, to generate a first set of variant data; c) applying a variant quality score calibration tool with a truth sensitivity threshold to remove false-positive variants having a sensitivity lower than the threshold and background variants from the first set of variant data so as to obtain a second set of variant data; d) removing synonymous variants from the second set of variant data to obtain a third set of variant data; and e) identifying one or more deleterious variants from the third set of variant data using a gene burden analysis, optionally generating a fourth set of variant data.

Method of identifying a gene associated with a disease or pathological condition of the disease

One embodiment is a method of treating cancer. The method includes administering a therapeutically effective amount of a compound to a patient. The compound is represented by Formula I: 

Methods of treating cancer

The administration of a compound advantageously efficacious as ROS1 inhibitor and its effect on subjects with cancer includes administering a compound having certain structural components such as a quinoline moiety in the backbone and at least one tertiary amine containing moiety in a side chain as well as heteroatoms, in particular oxygen atoms, present in the backbone and the side chain for treating a subject suffering from a disease such as cancer. The presence of such structural components allows for an advantageous interaction with the ROS1 kinase domain, in particular with the hinge region. The administered compounds represent a highly promising opportunity in particular for patients bearing ROS1-dependent cancer. A method for targeting tumor cells harboring an abnormality in ROS1 gene includes contacting a cell with compounds of the present invention as well as pharmaceutical compositions comprising such compounds.

ROS1 inhibitor and its use

One embodiment relates to a method of treating lung cancer by administering a compound of formula I to a patient. Another embodiment relates to a method of treating cancer with a KRAS mutation that includes administering to a patient the compound with the following formula I: 

Method of treating lung cancer

One example embodiment relates to a method of treating non-small cell lung cancer by administering a compound of formula (I) to a patient. Another example embodiment relates to a method of inhibiting progress of tumor growth in a patient with cancer, wherein tumor cells of the cancer have a mutant V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, and the method includes administering to the patient the compound with the following formula I: 

The present invention provides methods for treatment of a RAS-positive disease, in particular KRAS-positive non-small cell lung cancer as well as a method for potentiating the apoptotic activity of a PDE&#x3b4; inhibitor by combining the PDE&#x3b4; inhibitor with a direct autophagy inhibitor. The PDE&#x3b4; inhibitor is preferably, but not exclusively, deltarasin, and the direct autophagy inhibitor is in particular 3-methyladenine. Further provided by the present invention are a kit and a pharmaceutical composition comprising the PDE&#x3b4; inhibitor and a direct autophagy inhibitor. The methods of the present invention in particular provide a new treatment option for RAS-positive diseases such as KRAS-positive non-small cell lung cancer allowing for an increased apoptotic activity of the PDE&#x3b4; inhibitor by simultaneously blocking its 'tumor protective' autophagy.

Combination treatment of RAS-positive diseases with PDE-&#x3b4; inhibitor and direct autophagy inhibitor

A compound suitable for treating cancer, in particular NSCLC, inhibits activity of oncogenic ROS1 kinase and ALK kinase. The compound has certain structural components such as a quinoline moiety in the backbone and at least one phenyl-containing moiety in a side chain with a hydrophobic substituent attached to the backbone via an up to 6-membered linking group as well as a further hydrophobic moiety. The presence of the structural components allows for an advantageous interaction with the ROS1 kinase domain and, further, with the ALK kinase domain. Hence, said compound represents a highly promising opportunity for patients bearing ROS1- or ALK-dependent cancer. A composition, in particular a pharmaceutical composition, includes the compound. A method for targeting cancer cells harboring an abnormality in ROS1 gene or ALK gene includes contacting a cell with the compound.

Oncogenic ROS1 and ALK kinase inhibitor

The present invention provides a compound that inhibits activity of oncogenic ROS1, a composition comprising said compound. The present invention also provides the use of said composition for treating cancer.

Growing community of inventors

Macau, China

Xiao Jun Yao