Combination of two drugs disrupts cancer cells' ability to survive DNA damage, study finds

Medical News | October 14, 2019

In continuing efforts to find novel ways to kill cancer cells, researchers at the University of Maryland School of Medicine (UMSOM) have identified a new pathway that leads to the destruction of cancer cells. The new finding, recently published in the journal PNAS, could pave the way for the broader use of a class of anticancer drugs already on the market. These drugs, known as PARP inhibitors, are currently approved by the FDA to treat only a limited group of breast and ovarian cancers associated with BRCA gene mutations. In a proof of concept study, the researchers demonstrated that combining a PARP inhibitor with a DNA methyltransferase (DNMT) inhibitor delivered a one-two punch to non-small cell lung cancer tumors, which are normally not associated with mutations in BRCA genes. The research, conducted in mouse models and cell lines, outlines the mechanistic action of the combination. The DNMT inhibitor triggers an effect that mimics a BRCA mutation in the cancer cell so the cell responds to the lethal effects of the PARP inhibitor, which prevents repair of damage to a tumor cell's DNA, triggering cell death. Those who inherit two copies of a normal BRCA gene enjoy protection from DNA damage that can cause healthy cells to turn malignant. Those who inherit a mutation in this gene, however, have a higher risk of breast and ovarian cancer (in women) and prostate cancer (in men). Researchers have previously demonstrated that tumors that share molecular features of BRCA-mutant tumors – those with so-called "BRCAness" – respond to PARP inhibitor drugs designed to target tumors that arise from BRCA mutations. This new study from UMSOM is the first to demonstrate that cells can be induced to have a BRCAness phenotype or gene expression that is not the result of a mutation by treating them with the DNA methyltransferase inhibitor drug.

Spotlight

Most medications can be labeled as “one-size-fits-all.” We use the same drugs at the same doses and frequencies as others. Although practical, this is not ideal and might lead to undesired responses.

Spotlight

Most medications can be labeled as “one-size-fits-all.” We use the same drugs at the same doses and frequencies as others. Although practical, this is not ideal and might lead to undesired responses.

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XtalPi and EDDC collaborate in AI-empowered drug discovery program for Non-Small Cell Lung Cancer

XtalPi Inc. | December 20, 2022

XtalPi, a pioneering pharmaceutical technology company powered by artificial intelligence and automation, announced a strategic collaboration with the Experimental Drug Development Centre Singapore's national platform for drug discovery and development hosted by the Agency for Science, Technology and Research of Singapore to discover novel treatment candidates for non-small cell lung cancer. Lung cancer is the second most common cancer and the leading cause of cancer death worldwide. NSCLC accounts for over 80% of all lung cancer cases and its incidence continues to increase globally. The estimated global market size for NSCLC therapeutics will exceed USD20 billion by 2027, according to Research and Markets. Despite increasing interest and investment in drug research, there remains significant unmet needs for effective targeted therapy options for NSCLC patients to achieve better outcomes. In this collaboration, XtalPi joins forces with EDDC to apply its AI technology, automation platform, and expert domain knowledge to discover promising candidates against a NSCLC target chosen by EDDC. XtalPi will leverage its quantum physics and AI-driven platform to generate and screen through millions of molecules in de novo drug design. The predicted top-performing molecules with desirable drug properties will be validated and optimized in its robotics-powered synthesis and testing lab through iterations. EDDC will offer valuable insight and data on the novel NSCLC target, further accelerating the drug discovery process and propelling the program towards development. "We are delighted to establish this strategic collaboration with EDDC. XtalPi is committed to serving patients globally by advancing the speed, scale, novelty, and success rate of drug R&D with AI and automation. Through this partnership, we hope to continue expanding our collaborations with top-tier research institutes in the booming Pan-Asia biotech community, drive the quick translation of new discoveries into much-needed therapeutics, and contribute to the improved health and longevity of patients in Asia and around the world." Dr. Shuhao Wen, co-founder and chairman of XtalPi Professor Damian O'Connell, Chief Executive Officer of EDDC, comments: "We are excited to partner XtalPi in the translation of science and research into effective and targeted therapies that enable the treatment of cancer. With XtalPi's expertise in AI and automation technologies, we are confident that this collaboration will accelerate the development of potential targeted therapy options for NSCLC patients, which are very much needed." About XtalPi Founded in 2014, XtalPi founders recognized a common hurdle in drug development having to do with solid polymorphism, which could be successfully tackled with quantum physics predictions. Since then, XtalPi has maintained its focus on identifying and then attacking traditional bottlenecks in biopharmaceutical R&D through innovative technologies. Through considerable capital investments in automation and personnel, XtalPi now has four locations worldwide and employs approximately 1000 employees.

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Cambrex Announces the Acquisition of Snapdragon Chemistry

Cambrex | January 24, 2023

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Eyenovia, Inc. | November 30, 2022

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