Ovarian cancer (OC) is the fifth most common cause of cancer death in women. Although significant progress has been made in the treatment of OC, the majority of patients experience disease recurrence and receive second-line and sometimes several lines of treatment. Here we review the options available for the treatment of recurrent disease and discuss how different agents are selected, combined and offered in a rationale sequence in the context of multidisciplinary care. We reviewed published work between 1990 and 2013 and meeting abstracts related to the use of chemotherapy and surgery in patients with recurrent ovarian cancer. We discuss treatment regimens, efficacy endpoints and safety profiles of the different therapies. Platinum-based drugs are the most active agents and are selected on the basis of a probability of response to retreatment. Nonplatinum-based chemotherapy regimens are usually given in the 'platinum-resistant' setting and have a modest effect on outcome. Molecular targeted therapy of ovarian cancer given alone or integrated with chemotherapy is showing promising results. Many patients are now receiving more than one line of therapy for recurrent disease, usually platinum based until platinum resistance emerges. The sequential use of chemotherapy regimens and the incorporation of molecularly targeted treatments, either alone or in combination with chemotherapy, have over the last decade significantly extended the median survival of patients with ovarian cancer.

Growth Factor Receptor. NTRK1 was originally isolated from a colorectal carcinoma (CRC) sample as component of a somatic rearrangement (TPM3-NTRK1) resulting in expression of the oncogenic chimeric protein TPM3-TRKA, but there has been no subsequent report regarding the relevance of this oncogene in CRC. The KM12 human CRC cell line expresses the chimeric TPM3-TRKA protein and is hypersensitive to TRKA kinase inhibition.We report the detailed characterization of the TPM3-NTRK1 genomic rearrangement in KM12 cells and through a cellular screening approach, the identification of NMS-P626, a novel highly potent and selective TRKA inhibitor. NMS-P626 suppressed TPM3-TRKA phosphorylation and downstream signaling in KM12 cells and showed remarkable antitumor activity in mice bearing KM12 tumors.Finally, using quantitative reverse transcriptase PCR and immunohistochemistry (IHC) we identified the TPM3-NTRK1 rearrangement in a CRC clinical sample, therefore suggesting that this chromosomal translocation is indeed a low frequency recurring event in CRC and that such patients might benefit from therapy with TRKA kinase inhibitors.

Background: Breast cancer (BC) subtypes have different survival and response to therapy. We studied predictors of central nervous system metastases (CNS-M) and outcome after CNS-M diagnosis according to tumor subtype.