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Using synthetic lethality st ∏rategy to target tumor ce ↔γlls with DNA damage rep★'™air defects
Science Pipeline Technology
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Synthetic Lethality
Synthetic lethality is derived from a <↕±"genetic concept. In 1922,☆♦₩ Calvin Bridge, a geneticist at Col¶★umbia University, was studying$<δ Drosophila melanogaster. He disco÷δvered that combinations of several muta¥¶$tions induced lethali≈™®ty, while flies were viable w"∞§ ith any single gene mutatiδγπon. Twenty-four years later, Theod★ ∏→ore Dobzhansky, also working ←™α at Columbia University, u♥β™‌sed the term "synthetic lethal&★↑©quot; to describe these genetic in≈Ωteractions. Till now, t׶≠γhe definition of synthetic lethality isδ± well beyond the classical genetic inte÷©α≥ractions, as it refers to cell death ca÷πΩ¶used by simultaneous inhibitio‌★n of two non-lethal genes'← &.
DNA Damage Repair
In response to DNA damage¶♥ ≈, DNA damage repair (DDR)  ‌•machinery senses and repairs DN£ ©A lesions. Since the lδ↕&♦ack of DDR leads to the aΩ∑ccumulation of DNA lesions, w ¶hich eventually causes g→βλαenomic instability and tumo≥♣rigenesis, many DDR factors p♠ &lay an important role in tumor sup★α♥pressors. Hence, elucidating ₽ the mechanisms of DDR facilitatesβ✘ the development of no"​•vel cancer therapies. ♣
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Potential cancer therapeutic tar≈β'gets
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Oncogene
An oncogene is a gene t"" hat has the potential t∞¥o cause cancer. In tumor♣α  cells, these genes are often mutated, ♦≠☆or expressed at high levels.
Targeted Therapy
PARP inhibitors are the ✔¶first examples of synthetic lethal ★€ ​targeting in a population of×    patients with mutations in the t♣↑≈umor suppressor gene BRCA.
Tumor Suppressor Gene
A tumor suppressor gene is a≤δ gene that regulates a cell durin≤ g cell division and rep✘♣‍lication. When a tumor ×₩® suppressor gene is mut ® ♦ated, it results in a loss or reduc€φtion in its function. In combination wi₩€th other genetic mutations"‍♦, this could allow the ceα<ll to grow abnormally.
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