Purpose: The 8p12-p11 locus is frequently amplified in squamous cell lung cancer (SQLC); the receptor tyrosine kinase fibroblast growth factor receptor 1 (FGFR1) being one of the most prominent targets of this amplification. Thus, small molecules inhibiting FGFRs have been employed to treat FGFR1-amplified SQLC. However, only about 11% of such FGFR1-amplified tumors respond to single-agent FGFR...

A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker...

Drug resistance remains a major challenge in achieving cures cancer patients. Cabazitaxel has shown the ability to overcome drug induced by paclitaxel and docetaxel; however, substantially high toxicity been observed patients receiving this agent, which compromises its efficacy. We have previously demonstrated that polymeric platform (termed cabazitaxel-NPs) encapsulating oligolactide-cabazitax...

Hailed as a major step forward in the effort to develop targeted cancer therapies, a recently approved drug for the most common type of skin cancer has been a mixed blessing for patients. Although the initial response is usually dramatic, the tumors often recur as the cancer becomes resistant to treatment. Now researchers at the School of Medicine have identified a second way to block the activ...

Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitors, but drug resistance invariably emerges. To elucidate mechanisms of acquired drug resistance, we performed systematic genetic and histological analyses of tumor biopsies from 37 patients with drug-resistant non-small cell lung cancers (NSCLCs) carrying EGFR mutations. All d...

the high CISs found only in the PLX4720-resistant tumors. Further characterization revealed four transposon sites in the first intron of ERAS, with an integration pattern signifying gene activation. The PLX4720-resistance conferring phenotype was confirmed in human melanoma cell lines ectopically expressing ERas. Further mechanistic studies revealed that ERAS inactivation of BAD (BCL2-associate...

The objective of this study was to develop a rapid in vitro method for predicting the response of human tumors to anticancer drugs. In this study an attempt was made to correlate the drug effects on the relative incorporation of (3H) thymidine (ThdR) into DNA with the sensitivity of tumor cells to that drug. The results of the study indicate that following treatment of the cells with adriamycin...

One of the main and distinctive features of malignant tumors that considerably restrict the efficacy of cancer therapy is their ability to progress towards the appearance of drug resistance, invasion and metastatic spread of cancer cells. In fact, tumor metastasis remains the major cause of death for cancer patients. At the same time tumor drug resistance results in low efficacy of anticancer a...

Eribulin mesylate was developed as a potent microtubule-targeting cytotoxic agent to treat taxane-resistant cancers, but recent clinical trials have shown that it eventually fails in many patient subpopulations for unclear reasons. To investigate its resistance mechanisms, we developed a fluorescent analog of eribulin with pharmacokinetic (PK) properties and cytotoxic activity across a human ce...

Chemotherapy resistance of tumors is an important biological and clinical problem. Studies Troni many tumor types have indicated that resistance may he hased on multiple genetic pathways. Human male (¡ermacell tumors (GCTs) are an especially good model system to study the genetic hasis of tumor sensitivity and resistance to chemotherapy. GCTs are exquisitely sensitive to treatment with DNA-dam...