According to the American Association ××× statistics, this year, about 268,000 women are diagnosed with breast cancer, of which 15% -20% with triple negative breast cancer (TNBC). Standard treatment for a patient is TNBC neoadjuvant chemotherapy followed by surgical excision. Modern chemotherapy is very effective for nearly half of the triple-negative breast cancer patients. However, the remaining half of women do not respond to neoadjuvant chemotherapy, there is no approved treatment to improve their prognosis.
Recently, researchers at the MD Anderson ××× center of University of Texas found that triple negative breast cancer (TNBC) cells develop resistance to first-line or neoadjuvant chemotherapy, not by obtaining permanent adaptation, but briefly molecular pathways open cell protection. In these pathways are activated, there is a metabolic process known as oxidative phosphorylation, which helps researchers to develop small molecule drug targeting.
The study was published in the "Science Translational Medicine" magazine. The study also found a weakness, may provide a new treatment option for resistant TNBC.
Corresponding Author, professor of radiation oncology experiment Helen Piwnica-Worms, said: "For female patients chemotherapy is not completely reacted, the risk of recurrence and mortality of this disease is much higher."
Only by understanding how cancer cells develop resistance, researchers to find new and better target for the treatment of drug-resistant disease. TNBC cells in order to study how resistant to treatment, researchers use the registered patient tumor samples, creating a source of xenograft patients (pDXS) mouse model.
Piwnica-Worm team found several PDX models, which initially respond to chemotherapy, but eventually gave rise to drug resistance and restore tumor growth. However, if you stop treatment, residual tumor sensitive to chemotherapy again, indicating that resistance is temporary.
Under the microscope, the tumor showed significant changes during treatment, but prior to regeneration and treatment of tumors is similar. In addition, analysis of individual tumor cells showed heterogeneity of tumor cells after treatment remains unchanged, indicating that chemotherapy does not select a small resistant cells.
Characterization of gene expression changes discloses a group of activated passage resistance as part of the state, which passage is closed when the chemotherapy was discontinued. The researchers demonstrated that these molecular changes are reflected in many of biopsies taken from patients.
In order to find new therapeutic targets, researchers have found that these cells are dependent on oxidative phosphorylation to produce energy. In the treatment of mice treated with PDX IACS-10759 after chemotherapy, researchers observed synergistic effects, suggesting sequential therapy and chemotherapy IACS-10759 treatment can extend the reaction time. IACS-10579 is currently undergoing clinical trials in hematology and various types of entities ×××.
Piwnica-Worms, said: "Our study provides a compelling rationale to define the characteristics of other triple negative breast cancer can survive after chemotherapy treatment, so that you can develop combination therapies to eradicate this disease we hope. after avoided the use of the drug in patients with chemotherapy, instead of using targeted therapy in order to reduce unnecessary treatment and serious side effects. "more Journal of the American Medical Association click Browse.
References:
[1] Triple negative Breast cancers CAN ADOPT Reversible State that IS resistant to Chemotherapy
文章来源：生物探索