https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)61865-0.pdf

Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jps.20178

Antibody pharmacokinetics and pharmacodynamics.

Purpose Preclinical studies in ErbB2-positive cell lines demonstrated a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade is more effective than a single agent alone. EGF104900 compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC). Patients and Methods Patients with ErbB2-positive MBC who experienced progression on prior trastuzumab-containing regimens were randomly assigned to receive either lapatinib alone or in combination with trastuzumab. The primary end point was progression-free survival (PFS). Secondary efficacy end points included overall response rate (ORR), clinical benefit rate (CBR; complete response, partial response, and stable disease for ≥ 24 weeks), and overall survival (OS). Results In the intent-to-treat population (N = 296) who received a median of three prior trastuzumab-containing regimens, the combination of lapatinib with trastuzumab w...

Randomized Study of Lapatinib Alone or in Combination With Trastuzumab in Women With ErbB2-Positive, Trastuzumab-Refractory Metastatic Breast Cancer

Hepatocellular carcinoma (HCC) is a leading cause of death among cirrhotic patients and has become a major health problem in developed countries. There is an elemental understanding of the genes and signaling pathways involved in the initiation and progression of this neoplasm. The current hypothesis of the HCC cell origin includes both somatic cells (hepatocytes) and stem cells/progenitor cells. Unlike that in other malignancies such as breast, brain, or hematopoietic cancers, the implication of cancer stem cells in HCC pathogenesis is not yet supported by consistent data. Analysis of somatic genetic alterations and gene expression profiles in HCC samples has provided relevant information on the genes involved in hepatocarcinogenesis, pinpointing a seminal molecular classification of the disease. Nonetheless, a comprehensive genomic analysis of HCC samples using high-resolution platforms in precisely annotated HCCs is clearly needed. Recent data have identified different signaling pathways in liver carcinogenesis (e.g., Wnt-betaCatenin, Hedgehog, tyrosine kinase receptor-related pathways), providing an important potential source of novel molecular targets for new therapies. This review summarizes the most relevant information regarding structural and functional alterations in HCC and describes some of the key signaling pathways implicated in hepatocarcinogenesis.

I. C. Henderson

Papers

Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer.