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PARP inhibitors have shown promising clinical activities for patients with BRCA mutations and are changing the landscape of ovarian cancer treatment. However, the therapeutic mechanisms of action for PARP inhibition in the interaction of tumors with the tumor microenvironment and the host immune system remain unclear. We find that PARP inhibition by olaparib triggers robust local and systemic antitumor immunity involving both adaptive and innate immune responses through a STING-dependent antitumor immune response in mice bearing Brca1-deficient ovarian tumors. This effect is further augmented when olaparib is combined with PD-1 blockade. Our findings thus provide a molecular mechanism underlying antitumor activity by PARP inhibition and lay a foundation to improve therapeutic outcome for cancer patients.
This article was published in the following journal.
Name: Cell reports
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Stimulator of interferon genes (STING) is a key regulator of type I interferon and pro-inflammatory responses during infection, cellular stress, and cancer. Here, we reveal a mechanism for how STING ...
Recently, clinical development of PARP inhibitors (PARPi) expanded from using them as a single agent to combining them with DNA-damaging therapy to derive additional therapeutic benefit from stimulate...
In tumors with a defect in the homologous recombination (HR) pathway, double-strand break repair is partly impaired. Patients with HR deficient tumors benefit from therapies that induce DN...
Of the approximately 21,000 cases of ovarian cancer diagnosed annually in the U.S, ten percent are attributed to hereditary syndromes, most commonly the result of mutations in the breast c...
Olaparib has demonstrated preliminary efficacy in metastatic castration-resistant prostate cancer. In a trial of 49 evaluable patients treated with olaparib, 11 / 49 experienced a PSA resp...
The purpose of the study is to investigate the effectiveness of a sun lotion containing a specific Jellyfish sting inhibitor versus regular sun lotions as controls. In addition, to investi...
The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced breast cancer and for whom ...
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
Test for cell-mediated antitumor immunity and related serum blocking factors based on the finding that leukocytes from cancer patients, but not from controls, when mixed in vitro with antigenic extracts of tumors of the same histological type, undergo a diminution in their normal adherence to glass surfaces. Sera from tumor-bearing patients block the LAI reaction of their own leukocytes or those of other patients with the same type of tumor.
Arthropods of the order Scorpiones, of which 1500 to 2000 species have been described. The most common live in tropical or subtropical areas. They are nocturnal and feed principally on insects and other arthropods. They are large arachnids but do not attack man spontaneously. They have a venomous sting. Their medical significance varies considerably and is dependent on their habits and venom potency rather than on their size. At most, the sting is equivalent to that of a hornet but certain species possess a highly toxic venom potentially fatal to humans. (From Dorland, 27th ed; Smith, Insects and Other Arthropods of Medical Importance, 1973, p417; Barnes, Invertebrate Zoology, 5th ed, p503)
Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.
Phenomenon of cell-mediated immunity measured by in vitro inhibition of the migration or phagocytosis of antigen-stimulated LEUKOCYTES or MACROPHAGES. Specific CELL MIGRATION ASSAYS have been developed to estimate levels of migration inhibitory factors, immune reactivity against tumor-associated antigens, and immunosuppressive effects of infectious microorganisms.
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...
Track and monitor developments in breast cancer research and commercial development. Follow the tabs above to read the latest global news, research, clinical trials on breast cancer and follow companies active in the development of breast cancer tr...
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