Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. Multidrug resistance-associated proteins (MRPs) play an important role in the process of MDR. As an ATP-binding cassette (ABC) transporter superfamily, MRPs are selective and specific drug efflux pumps. In this paper, physiological characteristics, structural characteristics and resistance profile of MRPs and the associated reversal studies are reviewed.

The epidermal growth factor receptor (EGFR) provides a rational target for cancer therapy as it is commonly overexpressed in a variety of solid tumors, and its deregulation is correlated with resistance to chemotherapy and radiotherapy and a poor prognosis. Cetuximab (C255), a specific monoclonal antibody directed against EGFR, is synergistic with chemotherapy and radiotherapy and has been licensed for the treatment of irinotecan refractory colorectal cancer (CRC) and squamous cell cancer of the head and neck (SCCHN), which express EGFR. In addition, the clinical trials about cetuximab for the treatment of non-small cell lung cancer (NSCLC), breast and pancreas carcinoma are ongoing, and cetuximab has been proven to a novel strategy for the treatment of cancer with the overexpression of EGFR.

Multidrug resistance(MDR)of tumor cells has become the main impediment that influence the curative effect of cancer chemotherapy. Although there are many mechanisms can generate the multidrug resistance, the overexpression of P-glycoprotein encoded by the multidrug resistance-1(mdr1) gene is the main cause in the formation of MDR. Seaching for innocuous and effective reversal of MDR is not only a method of improving the efficiency of cancer chemotherapy but also the problem desiderated to be resolved in chemotherapy domain.

Sorafenib,a novel oral multikinase inhibitor,targts on serine/threonine kinase and tyrosine kinases receptor of the tumor cells and vasculature.So Sorafenib can inhibit the tumor cell proliferation and revascularization.400 mg sorafenib administered twice a day is chosen as the recommended dosage for several phase Ⅰ studies,and it shows broad-spectrum antitumor activity in renal cancer,hepatocellular carcinoma,melanoma and non-small-cell lung cancer(NSCLC)in phase Ⅱ and Ⅲ clinical trials.Now FDA has approved the usage of sorafenib in renal cancer therapy.

EGFR/HER-2 is an attractive therapeutic target for solid tumors.Lapatinib is an orally administered dual inhibitor of EGFR/HER-2 tyosine kinases.Preclinical experiments in vitro and in vivo models indicate that lapatinib is active against various solid tumors.Phase Ⅰ trials have shown an acceptable adverse event.Phase Ⅱand Ⅲ trials demonstrate the promising results for the treatment of metastatic,refractory,inflammatory,or brain metastatic breast cancer.With the further developments of biology,the molecular targeted chemotherapy becomes a novel adjuvant therapy for advanced breast cancer patients.

An endogenous suppressor of apoptosis, the inhibitor of apoptosis proteins(IAP) plays a key role in the occurrence and progression of cancer. In recent years cancer researches have been focused on gene-specific inhibitors with IAP as the target, so as to seek gene therapeutic strategies of less toxicity and higher efficiency. As members of IAP family, survivin and livin are over-expressed in tumors. Meanwhile, Smac can directly inhibit IAP. These findings suggest a promising alternative strategy for developing novel anticancer therapies.-

A large number of natural acetogenins have been isolated from se veral genera of the plant family Annonaceae. Many of these compounds have very p otent and diverse biological effects such as cytotoxic, antitumour, anti-malari al, pesticidal and anti-feedant activities. This paper reviews research finding s about the effects of annonaceous acetogenins on antitumor, MDR, mechanism of ac tion, structural-activity relationships etc.

AIM We found in experiment that the relation of cell number-OD in MTS cytotoxicity assay is non-linearity. In this paper we probe into the relations of cell number-OD and drug dose-inhibition rate. METHODS Cells HL-60 and Raji were used in this experiment. Assay on the relation of cell number-OD: Cells of different concentrations were seeded into 96 well plates. OD was read at 490 nm after incubating with MTS for 1～5 hour. The regression curves were estimated from the data with the software SPSS 11.0. Cytotoxicity assay: Cells were seeded into 96 well plate and incubated with drug of different doses for 72 hours. OD was read at 490 nm after incubating with MTS for 3 hour. The regression curves were estimated from the data with the software SPSS 11.0. RESULTS The cubic curves fit well the relations of cell number-OD of the 2 strains of cells at 5 time points and the coefficient R2 of these cubic curves is 0.997～1.000, greater than the R2 0.938～0.993 of linear model. For the relations of dose-inhibition rate, the cubic curves also have best fitness and their R2 is 0.998～1.000 greater than the R2 0.948～0.987 of linear model of logarithm dose-probit. CONCLUSION For the relations of cell number-OD in MTS cytotoxicity assay, the fitness of cubic curves are better than the linear model. A more accurate IC 50 would be obtained by the cubic curve equation than by probit regression that is in common use.

Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.