Category: Oncology

Prostate cancer discovery may make it easier to kill cancer cells

pjgrier Hot Topics in Research, Oncology, Prostate, Uncategorized

Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth
Abstract:
Prostate cancer is the second leading cause of cancer death in American men, and curing metastatic disease remains a significant challenge. Nearly all patients with disseminated prostate cancer initially respond to androgen deprivation therapy (ADT), but virtually all patients will relapse and develop incurable castrationresistant prostate cancer (CRPC). A high-throughput RNAi screen to identify signaling pathways regulating prostate cancer cell growth led to our discovery that checkpoint kinase 2 (CHK2) knockdown dramatically increased prostate cancer growth and hypersensitized cells to low androgen levels. Mechanistic investigations revealed that the effects of CHK2 were dependent on the downstream signaling proteins CDC25C and CDK1. Moreover, CHK2depletion increased androgen receptor (AR) transcriptional activity on androgen-regulated genes, substantiating the finding that CHK2 affects prostate cancer proliferation, partly, through the AR. Remarkably, we further show that CHK2 is a novel ARrepressed gene, suggestive of a negative feedback loop between CHK2 and AR. In addition, we provide evidence that CHK2 physically associates with the AR and that cell-cycle inhibition increased this association. Finally, IHC analysis of CHK2 in prostate cancer patient samples demonstrated a decrease in CHK2 expression in high-grade tumors. In conclusion, we propose that CHK2 is a negative regulator of androgen sensitivity and prostate cancer growth, and that CHK2 signaling is lost during prostate cancer progression to castration resistance. Thus, perturbing CHK2 signaling may offer a new therapeutic approach for sensitizing CRPC to ADT and radiation.
 
Cancer Research. 12/1/2015, Vol. 75 Issue 23, p5093-5105. 13p.

Practical experiences with eribulin in patients with metastatic breast cancer

pjgrier Breast, Hot Topics in Research, Oncology

Practical experiences with eribulin in patients with metastatic breast cancer
Background There is currently no standard therapy for women with metastatic or locally recurrent breast cancer. The microtubule polymerization inhibitor eribulin, approved in March 2011, is the first monochemotherapy with a proven survival benefit and tolerable toxicity in this patient group.
Patients and methods Using a retrospective analysis of 27 mostly heavily pretreated patients in two large German breast cancer centers, the efficacy and tolerability of eribulin in daily practice were compared with the results of the pivotal EMBRACE and 301 studies.
Results Despite the patients being older and having more advanced disease, the retrospective analysis showed a comparable progression-free survival of 3.7 months. When eribulin was used in an early-line treatment, the progression-free survival observed was 7 weeks longer compared with use in a late-line therapy. The differences in tolerability were not significant.

Anti-Cancer Drugs
Issue: Volume 27(2), February 2016, p 112–117

Management of Pulmonary Nodules by Community Pulmonologists

pjgrier Hot Topics in Research, Lung, Oncology

Management of Pulmonary Nodules by Community Pulmonologists
BACKGROUND: Pulmonary nodules (PNs) are a common reason for referral to pulmonologists. Th e majority of data for the evaluation and management of PNs is derived from studies performed in academic medical centers. Little is known about the prevalence and diagnosis of PNs, the use of diagnostic testing, or the management of PNs by community pulmonologists. METHODS: Th is multicenter observational record review evaluated 377 patients aged 40 to 89 years referred to 18 geographically diverse community pulmonary practices for intermediate PNs (8-20 mm). Study measures included the prevalence of malignancy, procedure/test use, and nodule pretest probability of malignancy as calculated by two previously validated models. Th e relationship between calculated pretest probability and management decisions was evaluated. RESULTS: Th e prevalence of malignancy was 25% (n 5 94). Nearly one-half of the patients (46%, n 5 175) had surveillance alone. Biopsy was performed on 125 patients (33.2%). A total of 77 patients (20.4%) underwent surgery, of whom 35% (n 5 27) had benign disease. PET scan was used in 141 patients (37%). Th e false-positive rate for PET scan was 39% (95% CI, 27.1%-52.1%). Pretest probability of malignancy calculations showed that 9.5% (n 5 36) were at a low risk, 79.6% (n 5 300) were at a moderate risk, and 10.8% (n 5 41) were at a high risk of malignancy. Th e rate of surgical resection was similar among the three groups (17%, 21%, 17%, respectively; P 5 .69). CONCLUSIONS: A substantial fraction of intermediate-sized nodules referred to pulmonologists ultimately prove to be lung cancer. Despite advances in imaging and nonsurgical biopsy techniques, invasive sampling of low-risk nodules and surgical resection of benign nodules remain common, suggesting a lack of adherence to guidelines for the management of PNs.
CHEST2015; 148(6): 1405 – 1414