Recent updated reports from the large adjuvant trials in HER2-positive breast cancer indicate that the remarkable benefits of adding trastuzumab to chemotherapy appear, so far, to be sustained rather than transient. Other studies show that even small, node-negative, HER2-positive tumors carry some risk of recurrence and might benefit from trastuzumab-based adjuvant therapy. Evaluations of HER2 test results have examined the benefit of trastuzumab in cancers that exhibit focally positive gene amplification and also have raised the question of whether the criteria that correlate HER2 positivity with trastuzumab benefit in the adjuvant setting may be different from the criteria that apply in the treatment of metastatic disease. New results from trials combining targeted agents in the treatment of metastatic breast cancer provide strong rationale for the current adjuvant trials. In addition, neoadjuvant studies lend further support for combining targeted agents and may also provide an optimal setting to identify biomarkers that correlate with patient outcome. A new generation of therapies, including novel targeted agents and vaccines, is moving forward in clinical development and will be incorporated into adjuvant regimens in the future.
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http://dx.doi.org/10.3816/CBC.2010.s.006 | DOI Listing |
J Transl Med
December 2024
Department of Thoracic Surgery, School of Clinical Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan University, No.7, Wei Wu Road, Jinshui District, Zhengzhou, Henan, 450003, China.
Background: The RAR-related orphan receptor alpha (RORA), a circadian clock molecule, is highly associated with anti-oncogenes. In this paper, we defined the precise action and mechanistic basis of RORA in ESCC development under hypoxia.
Methods: Expression analysis was conducted by RT-qPCR, western blotting, immunofluorescence (IF), and immunohistochemistry (IHC) assays.
Cell Mol Life Sci
December 2024
Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
Over the past few decades, microtubules have been targeted by various anticancer drugs, including paclitaxel and eribulin. Despite their promising effects, the development of drug resistance remains a challenge. We aimed to define a novel cell death mechanism that targets microtubules using eribulin and to assess its potential in overcoming eribulin resistance.
View Article and Find Full Text PDFCommun Biol
December 2024
Mayo Clinic, Rochester, MN, USA.
Antibody-drug conjugates (ADCs) are increasingly used in clinic for multiple indications and may improve upon the activity of parental antibodies by delivering cytotoxic payloads into target cells. This activity is predicated upon internalization to release the cytotoxic payloads intracellularly. Since binding of ADCs to their cell surface targets does not guarantee their internalization, we hypothesize that proteolysis targeting chimeras (PROTACs) could improve the activity of ADCs through forced internalization.
View Article and Find Full Text PDFSci Rep
December 2024
Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, 40127, Bologna, Italy.
This manuscript details the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CL, the main protease from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CL is essential for producing the proteins necessary for viral infection, which led to the COVID-19 pandemic. The ITC-based assay provided rapid and reliable measurements of 3CL activity, allowing for the direct derivation of the kinetic enzymatic constants K and k by monitoring the thermal power required to maintain a constant temperature as the substrate is consumed.
View Article and Find Full Text PDFBMJ Open Respir Res
December 2024
World Health Organization, Geneva, Switzerland.
Background: Tuberculosis (TB) poses a significant public health challenge in Guinea, with an estimated 22 000 TB cases in 2020; an estimated 6125 (28%) cases went undetected. We evaluated an intensified TB case finding strategy in Guinea which targeted customers who bought cough suppressants from pharmacies or drug outlets.
Methods: We involved 25 pharmacies and 25 drug outlets in Matoto, Conakry, Guinea.
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