Pharma Strategy Blog

Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits.

The sensitivity of the MMS and USS screening strategies is encouraging. Specificity was higher in the MMS than in the USS group, resulting in lower rates of repeat testing and surgery. This in part reflects the high prevalence of benign adnexal abnormalities and the more frequent detection of borderline tumours in the USS group. The prevalence screen has established that the screening strategies are feasible. The results of ongoing screening are awaited so that the effect of screening on mortality can be determined.

Inflammatory breast cancer is rare, but very aggressive. Options for patients with such tumours that are resistant to conventional treatments—anthracyclines, taxanes, and trastuzumab—are limited. In this phase II study, researchers assess the effectiveness of lapatinib, an orally taken reversible inhibitor of EGFR-tyrosine kinases, in patients with relapsed or refractory inflammatory breast cancer. Although no patient had a complete response to the drug, almost 40% had a partial response and, intriguingly, patients who were resistant to trastuzumab did not seem to exhibit cross-resistance to lapatinib, offering a glimmer of hope to patients who have failed previous therapy.

Per cent breast water was greatest during the ages when women are most susceptible to breast carcinogens, and was associated with weight, height, and mother's breast-tissue characteristics, and with serum concentrations of growth hormone: a breast mitogen that also mediates postnatal somatic growth. Mammographic density in middle age might partly be the result of genetic factors that affect growth and development in early life.

EGFR therapy and cetuximab in lung cancer following the publication of the FLEX study showing an improvement in survival of 1.2 months in the first-line setting for NSCLC

We generated in vivo gefitinib-resistance models in an adenocarcinoma xenograft model by serially passaging tumors in nude mice in presence of gefitinib until resistance was acquired. EMP-1 was identified as a surface biomarker whose expression correlated with acquisition of gefitinib resistance. EMP-1 expression was further correlated with lack of complete or partial response to gefitinib in lung cancer patient samples as well as clinical progression to secondary gefitinib resistance.

PTEN is an important tumor-suppressor gene associated with many cancers. Through expression profiling of glioblastoma tissue samples and prostate cancer xenografts, we identified a molecular signature for loss of the PTEN tumor suppressor in glioblastoma and prostate tumors. The PTEN signature consists of a minimum of nine genes, several of which are involved in various pathways already implicated in tumor formation. Among these signature genes, the most significant was an increase in insulin growth factor-binding protein 2 (IGFBP-2) mRNA.

Loss of expression of the TGF-β superfamily coreceptor, the type III TGF-β receptor (TβRIII or betaglycan), occurs in a broad spectrum of human cancers including breast, lung, ovarian, pancreatic, prostate, and renal cell cancer. TβRIII suppresses cancer progression in vivo, at least in part, by reducing cancer cell motility.

ARC 100 is an investigational agent whose mechanism of action is similar to other anti-tubulin drugs. Microtubulin-targeting drugs (e.g. taxanes, epothilones) act by inhibiting the activity of the spindle apparatus, an essential process allowing tumor cells to divide. These drugs are important components of chemotherapy for a variety of cancers, including tumors of the breast, lung, prostate, ovary, stomach, and head and neck. Unfortunately, resistance to these agents often develops, potentially due to upregulation of the efflux protein encoded by the mdr1 gene. Side effects of these drugs, notably myelosuppression, may also limit their utility. In addition, there is little activity against certain tumor types, e.g. pancreatic cancer.