Netrin-1, a laminin-related protein, is known to be involved in the nervous system development. Recently, Netrin-1's involvement in other processes such as cell adhesion, motility, proliferation, and differentiation that are important for the development of epithelial tissues has been described. In addition, Netrin-1 and its receptors, deleted in colorectal cancer and uncoordinated-5 homolog, have been linked to apoptosis and angiogenesis. Since these properties are essential for tumor development, Netrin-1 and its receptors have been reported to promote tumorigenesis in many types of cancers. Here, we review the Netrin-1 mediated regulation of cancer, its potential use as a biomarker, and the targeting of the Netrin-1 pathway to treat cancers.

PURPOSE Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition. METHODS MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641 ) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR−, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR− cohort. RESULTS Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR− cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events. CONCLUSION Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.

BackgroundAntivascular endothelial growth factor tyrosine kinase inhibitors have been used recently in the treatment of advanced differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC). Off-label sorafenib is used in Turkey with special permission by the Ministry of Health for this indication.Patients and methodsPatients with advanced DTC and MTC were retrospectively identified from the Turkish Ministry of Health database. Data on these patients were prospectively collected before permission is granted to use sorafenib.ResultsThirty patients with complete data were analyzed: 14 DTC (papillary number [n] =10; follicular n=4) and 16 MTC. The median age of the patients was 57 years (range: 28–79 years), and there were 18 males and 12 females. All DTC patients were iodine refractory and had received a median three doses of radioactive iodine (range: 1–7 doses). Sorafenib was used for a median of 12 months (range: 1–49 months). The overall response rate was 20%, all partial responses, with no complete response. The overall response rate was 14% in DTC and 25% in MTC patients. The median progression-free survival (PFS) was 17.1 months (95% confidence interval [CI]: 7.3–26.8) and overall survival (OS) was not reached. The 2-year PFS and OS were 39% and 68%, respectively. DTC and MTC patients had similar survival outcomes: median PFS of 21.3 months (95% CI: 5.8–36.7) versus 14.5 months (95% CI: 3.7–25.2), respectively (P=0.36), with the median OS not reached in either group (P=0.17). Tumor marker levels did not have any prognostic or predictive role. The toxicity profile was similar to that of other sorafenib trials.ConclusionSorafenib is an effective and well-tolerated treatment in advanced thyroid cancers.

Background: The aim of this study was to examine the cardiac effects of anthracycline therapy based on speckle-tracking echocardiography (STE) and to identify patients at risk for cardiotoxicity. Patients and Methods: The study included 35 breast cancer (BC) and 15 lymphoma patients who were treated with anthracycline-based chemotherapy. Conventional echocardiography and STE were performed 1 month prior to and 1 month after chemotherapy. Longitudinal strain analysis was performed via STE using automated functional imaging. Results: The ejection fraction (EF) and the fractional shortening values were significantly lower in the lymphoma group. There was a positive correlation between anthracycline dose and subclinical heart failure (p = 0.024). There was an increase in the myocardial performance index in both groups. After therapy, STE showed regional decreases in the longitudinal strain values in the BC group, but the global strain values did not differ. In the lymphoma group, the apical long-axis, the 4-chamber, and the global longitudinal strain values were significantly lower after therapy (p = 0.002, 0.041, and 0.004, respectively). The long-axis and global longitudinal strain values were significantly lower in the lymphoma patients with normal EF values (p = 0.01 and 0.05, respectively). Conclusion: Cardiotoxicity during the early phase of anthracycline treatment can be detected via STE prior to the observation of systolic function deterioration.

Efficacy of bevacizumab may be lower in obese patients. Among patients with Kras wild-type left-sided tumors treated with bevacizumab-based regimens, the prognosis could be worse for obese patients than that for non-obese patients. There is a need for prospectively designed studies of obese patients to prove the efficacy and dosages of bevacizumab in treatment of mCRC.