Prostate Cancer R...
Follow
Find
1.5K views | +0 today
Prostate Cancer Research Digest
Latest curated news on prostate cancer
Curated by Cancer Commons
Your new post is loading...
Your new post is loading...
Scooped by Cancer Commons
Scoop.it!

Inhibition of Protein Kinase C / Twist1 Signaling Augments Anti-Cancer Effects of Androgen Deprivation and Enzalutamide in Prostate Cancer

"Our findings indicate that PKC/Twist1 signaling contributes to castration resistance as well as enzalutamide resistance in prostate cancer, and suggest that therapeutics targeting PKC/Twist1 signaling, such as PKC inhibitors, represent a promising novel therapeutic strategy for prostate cancer, especially castration-resistant prostate cancer, when combined with enzalutamide."

Cancer Commons's insight:

Shiota M, Yokomizo A, Takeuchi A,  Imada K et al.

Clinical Cancer Res., Dec 18 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Rb Loss is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma

"Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. We examined the status of RB1, TP53 and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy number variation analysis and sequencing of formalin fixed paraffin-embedded specimens. Results: We found Rb protein loss in 90% (26/29) of small cell carcinoma cases with RB1 allelic loss in 85% (11/13) of cases. Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3/7) showed Rb protein loss. In contrast, only 7% (10/150) of primary high grade acinar carcinomas, 11% (4/35) of primary acinar carcinomas with neuroendocrine differentiation, and 15% (2/13) of metastatic castrate resistant acinar carcinomas showed Rb protein loss. Loss of PTEN protein was seen in 63% (17/27) of small cell carcinomas, with 38% (5/13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% (14/25) of small cell carcinomas, with 60% (6/10) of cases showing TP53 mutation.  Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by validated IHC assay. As Rb protein loss rarely occurs in high grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target."

Cancer Commons's insight:

Tan S,  Sood A, Rahimi H, Wang W et al.

Clinical Cancer Res., Dec 10 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

TMPRSS2:ERG Gene Fusion Predicts Subsequent Det... [J Clin Oncol. 2013] - PubMed - NCBI

"High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a precursor lesion of prostate cancer (PCa). The predictive value of ERG gene fusion in HGPIN for PCa was interrogated as a post hoc analysis in the context of a randomized clinical trial.The GTx Protocol G300104 randomly assigned 1,590 men with biopsy-diagnosed HGPIN to receive toremifene or placebo for 3 years or until a diagnosis of PCa was made on prostate biopsy. As part of this phase III clinical trial, a central pathologist evaluated biopsies of patients with isolated HGPIN at baseline and 12, 24, and 36 months of follow-up. ERG immunohistochemistry was performed on biopsies from 461 patients and evaluated for protein overexpression. ERG expression was detected in 11.1% of patients (51 of 461 patients) with isolated HGPIN. In the first year and during the 3-year clinical trial, 14.7% and 36.9% of 461 patients were diagnosed with PCa, respectively. Patients with ERG expression were more likely to develop PCa, with 27 (53%) of 51 ERG-positive and 143 (35%) of 410 ERG-negative patients experiencing progression to PCa (P = .014, Fisher's exact test). ERG expression was not associated with age, baseline PSA, Gleason score, or tumor volume.This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression. Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification."

.

Cancer Commons's insight:

Park K, Dalton JT, Narayanan R, Barbieri CE, et al.  

JCO, Dec 2 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Importance of 5α-Reductase Gene Polymorphisms on Circulating and Intraprostatic Androgens in Prostate Cancer

We report that five of the seven SRD5A markers differentially affect sex-steroid profiles of dihydrotestosterone and its metabolites in both the circulation and prostatic tissues of PCa patients. Remarkably, a 32% increase in intraprostatic testosterone levels was observed in the presence of the high-risk SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated predominantly with circulating levels of inactive glucuronides. Indeed, the rs12470143 SRD5A2 protective allele was associated with high circulating androstane-3α, 17β-diol 3-glucuronide (3α-diol-17G) levels as opposed to lower levels of both 3α-diol-17G and androsterone-glucuronide observed with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349 (V89L) risk variants, in strong linkage disequilibrium, were associated with higher circulating levels of 3α-diol-3G. The SRD5A2 rs676033 variant further correlated with enhanced intraprostatic exposure to 5α-reduced steroids (dihydrotestosterone and its metabolite 3β-diol). Similarly, the SRD5A1 rs166050C risk variant was associated with greater prostatic exposure to androsterone whereas no association was noted with circulating steroids. Conclusions. Our data support the association of 5α-reductase germline polymorphisms with the hormonal milieu in PCa patients. Further studies are needed to evaluate if these variants influence 5α-reductase inhibitor efficacy.

Cancer Commons's insight:

Levesque E, Laverdiere I, Lacombe L, Caron P, Rouleau M et al

Clinical Cancer Resrarch, Nov 26, 2013

 


more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Long-term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer

"Tasquinimod (Active Biotech) is an oral immunomodulatory, anti-angiogenic, and anti-metastatic agent that delayed metastatic disease progression in a randomized placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). Here, we report long-term survival with biomarker correlates from this trial. The survival observed in this trial of men with minimally symptomatic mCRPC suggests that the prolongation in PFS with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable risk:benefit ratio"

Cancer Commons's insight:

Armstrong AJ, Häggman M, Stadler WM, Gingrich JR et al. 

Clinicl Cancer Research, Nov 20, 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Metastatic castration-resistant prostate cancer reveals intrapatient similarity and interpatient heterogeneity of therapeutic kinase targets

Metastatic castration-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. The need to identify new actionable targets in CRPC is crucial as we begin to examine the resistance mechanisms related to androgen withdrawal. Here, we report an unbiased quantitative phosphoproteomic approach to identify druggable kinases in metastatic CRPC. These kinase activation patterns revealed intrapatient similarity and interpatient heterogeneity across a large panel of targets. Interestingly, these kinase activities are not a result of mutation but rather pathway activation within the tumors themselves. The observation that similar kinase activities are present in most if not all anatomically disparate metastatic lesions from the same patient suggests that CRPC patients may benefit from individualized, targeted combination therapies.

Cancer Commons's insight:

Drake JN, Graham NA, Lee JK, Stoyanova T et al.

PNAS, Nov 18, 2013

more...
No comment yet.
Rescooped by Cancer Commons from Lung Cancer Research Digest
Scoop.it!

Regulation of Heterochromatin Transcription by Snail1/LOXL2 During Epithelial-to-Mesenchymal Transition

"Although heterochromatin is enriched with repressive traits, it is also actively transcribed, giving rise to large amounts of noncoding RNAs. Although these RNAs are responsible for the formation and maintenance of heterochromatin, little is known about how their transcription is regulated. Here, we show that the Snail1 transcription factor represses mouse pericentromeric transcription, acting through the H3K4 deaminase LOXL2. Since Snail1 plays a key role in the epithelial-to-mesenchymal transition (EMT), we analyzed the regulation of heterochromatin transcription in this process. At the onset of EMT, one of the major structural heterochromatin proteins, HP1α, is transiently released from heterochromatin foci in a Snail1/LOXL2-dependent manner, concomitantly with a downregulation of major satellite transcription. Moreover, preventing the downregulation of major satellite transcripts compromised the migratory and invasive behavior of mesenchymal cells. We propose that Snail1 regulates heterochromatin transcription through LOXL2, thus creating the favorable transcriptional state necessary for completing EMT."

Cancer Commons's insight:

Millanes-Romero AHerranz NPerrera VIturbide A, et al. Molecular Cell. Nov 14, 2013.

more...
Cancer Commons's curator insight, November 14, 2013 1:35 PM

Millanes-Romero AHerranz NPerrera VIturbide A, et al. Molecular Cell. Nov 14, 2013.

Cancer Commons's curator insight, November 14, 2013 1:35 PM

Millanes-Romero AHerranz NPerrera VIturbide A, et al. Molecular Cell. Nov 14, 2013.

Rescooped by Cancer Commons from Lung Cancer Research Digest
Scoop.it!

Molecular Cell - HDAC5, a Key Component in Temporal Regulation of p53-Mediated Transactivation in Response to Genotoxic Stress

"Despite being one of the most well-studied transcription factors, the temporal regulation of p53-mediated transcription is not very well understood. Recent data suggest that target specificity of p53-mediated transactivation is achieved by posttranslational modifications of p53. K120 acetylation is a modification critical for recruitment of p53 to proapoptotic targets. Our data reveal that histone deacetylase 5 (HDAC5) binds to p53 and abrogates K120 acetylation, resulting in preferential recruitment of p53 to proarrest and antioxidant targets at early phases of stress. However, upon prolonged genotoxic stress, HDAC5 undergoes nuclear export. Concomitantly, p53 is acetylated at the K120 residue and selectively transactivates proapoptotic target genes, leading to onset of apoptosis. Furthermore, upon genotoxic stress in mice where HDAC5 expression is downregulated, the onset of apoptosis is accelerated in the highly vulnerable tissues. These findings suggest that HDAC5 is a key determinant of p53-mediated cell fate decisions in response to genotoxic stress."

Cancer Commons's insight:

Sen NKumari R, Singh MIDas S. Molecular Cell. Oct 10, 2013.

more...
Cancer Commons's curator insight, November 14, 2013 1:28 PM

Sen NKumari R, Singh MIDas S. Molecular Cell. Oct 10, 2013.

Cancer Commons's curator insight, November 14, 2013 1:29 PM

Sen NKumari R, Singh MIDas S. Molecular Cell. Oct 10, 2013.

Scooped by Cancer Commons
Scoop.it!

Microenvironmental Regulation of Tumor Progression and Metastasis

Microenvironmental Regulation of Tumor Progression and Metastasis | Prostate Cancer Research Digest | Scoop.it

"Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects."

Cancer Commons's insight:

Quail DF, Joyce JA. Nature Medicine. Nov 7, 2013.

more...
Cancer Commons's curator insight, November 8, 2013 1:51 PM

Quail DF, Joyce JA. Nature Medicine. Nov 7, 2013.

Cancer Commons's curator insight, November 8, 2013 1:51 PM

Quail DF, Joyce JA. Nature Medicine. Nov 7, 2013.

Rescooped by Cancer Commons from Lung Cancer Research Digest
Scoop.it!

Oncologists Lead on Reform, Ex CMS Head Says

Oncologists Lead on Reform, Ex CMS Head Says | Prostate Cancer Research Digest | Scoop.it

"Oncologists are at the forefront of payment and delivery reforms sweeping medicine today, a former head of Medicare said here Monday. Innovations in cancer care delivery -- such as oncology patient-centered medical homes -- are blazing the trail for all specialists, said Mark McClellan, MD, PhD, director of the Health Care Innovation and Value Initiative at the Brookings Institution in Washington."

Cancer Commons's insight:

Medpage Today | Nov 5, 2013

more...
Cancer Commons's curator insight, November 7, 2013 7:36 PM

Medpage Today | Nov 5, 2013

Cancer Commons's curator insight, November 7, 2013 7:36 PM

Medpage Today | Nov 5, 2013

Rescooped by Cancer Commons from Lung Cancer Research Digest
Scoop.it!

Selective Cancer Targeting with Prodrugs Activated by Histone Deacetylases and a Tumour-Associated Protease

"Eradication of cancer cells while minimizing damage to healthy cells is a primary goal of cancer therapy. Highly selective drugs are urgently needed. Here we demonstrate a new prodrug strategy for selective cancer therapy that utilizes increased histone deacetylase (HDAC) and tumour-associated protease activities produced in malignant cancer cells. By coupling an acetylated lysinegroup to puromycin, a masked cytotoxic agent is created, which is serially activated by HDAC and an endogenous protease cathepsin L (CTSL) that remove the acetyl group first and then the unacetylated lysine group liberating puromycin. The agent selectively kills human cancer cell lines with high HDAC and CTSL activities. In vivo studies confirm tumour growth inhibition in prodrug-treated mice bearing human cancer xenografts. This cancer-selective cleavage of the masking group is a promising strategy for the next generation of anticancer drug development that could be applied to many other cytotoxic agents."

Cancer Commons's insight:

Ueki N, Lee S, Sampson NS, Hayman MJ, et al. Nature Communications. Nov 5, 2013.

more...
Cancer Commons's curator insight, November 6, 2013 1:41 PM

Ueki N, Lee S, Sampson NS, Hayman MJ, et al. Nature Communications. Nov 5, 2013.

Cancer Commons's curator insight, November 6, 2013 1:43 PM

Ueki N, Lee S, Sampson NS, Hayman MJ, et al. Nature Communications. Nov 5, 2013.

Scooped by Cancer Commons
Scoop.it!

Use of Statins and the Risk of Death in Patients With Prostate Cancer

"Purpose: To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins. Patients and Methods: A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins. Results: During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively). Conclusion: Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis."

Cancer Commons's insight:

Yu O, Eberg M, Benayoun S, Aprikian A, et al. Journal of Clinical Oncology. Nov 4, 2013.

more...
No comment yet.
Rescooped by Cancer Commons from Lung Cancer Research Digest
Scoop.it!

A Pilot Study Using Next-Generation Sequencing in Advanced Cancers: Feasibility and Challenges

A Pilot Study Using Next-Generation Sequencing in Advanced Cancers: Feasibility and Challenges | Prostate Cancer Research Digest | Scoop.it

"New anticancer agents that target a single cell surface receptor, up-regulated or amplified gene product, or mutated gene, have met with some success in treating advanced cancers. However, patients' tumors still eventually progress on these therapies. If it were possible to identify a larger number of targetable vulnerabilities in an individual's tumor, multiple targets could be exploited with the use of specific therapeutic agents, thus possibly giving the patient viable therapeutic alternatives."

Cancer Commons's insight:

Weiss GJ, Liang WS, Demeure MJ, Kiefer JA, et al. PLOS One. Oct 2013.

more...
Cancer Commons's curator insight, October 31, 2013 3:26 PM
Weiss GJ, Liang WS, Demeure MJ, Kiefer JA, et al. PLOS One. Oct 2013.
Cancer Commons's curator insight, October 31, 2013 3:29 PM

Weiss GJ, Liang WS, Demeure MJ, Kiefer JA, et al. PLOS One. Oct 2013.

Scooped by Cancer Commons
Scoop.it!

Randomized, Placebo-Controlled, Phase III Trial of Sunitinib Plus Prednisone Versus Prednisone Alone in Progressive, Metastatic, Castration-Resistant Prostate Cancer

The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.

Cancer Commons's insight:

Michaelson MD, Oudard S, Ou Y-C, Lisa L et al

JCO, Dec 10, 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Visceral Disease in Castration-resistant Prostate C... [Eur Urol. 2013] - PubMed - NCBI

"Metastatic involvement of the viscera in men with advanced castration-resistant prostate cancer(CRPC) has been poorly characterised to date. In 359 CRPC patients treated between June 2003 and December 2011, the frequency of radiologically detected visceral metastases before death was 32%. Of the 92 patients with computed tomography performed within 3 mo of death, 49% had visceral metastases. Visceral metastases most commonly involved the liver (20%) and lung (13%). Median survival from diagnosis of visceral disease was 7.1 mo (95% confidence interval, 5.9-8.3). Survival was affected by the degree of bone involvement at detection of visceral disease, varying from 6.1 mo in men with more than six bone metastases to 18.2 mo in men with no bone metastases (p=0.001). Heterogeneity was noted in clinical phenotypes andprostate-specific antigen trends at development of visceral metastases. Visceral metastases are now more commonly detected in men with CRPC, likely due to the introduction of novel survival-prolonging treatments."

Cancer Commons's insight:

Pezaro CJ, Omlin A, Lorente D, Nava Rodrigues D

Eur Urol.  Nov 22, 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells

"The relationship between the cells that initiate cancer and the cancer stem-like cells that propagate tumors has been poorly defined. In a human prostate tissue transformation model, basal cells expressing the oncogenes Myc and myristoylated AKT can initiate heterogeneous tumors. Tumors contain features of acinar-type adenocarcinoma with elevated eIF4E-driven protein translation and squamous cell carcinoma marked by activated beta-catenin. Lentiviral integration site analysis revealed that alternative histological phenotypes can be clonally derived from a common cell of origin. In advanced disease, adenocarcinoma can be propagated by self-renewing tumor cells with an androgen receptor-low immature luminal phenotype in the absence of basal-like cells. These data indicate that advanced prostate adenocarcinoma initiated in basal cells can be maintained by luminal-like tumor-propagating cells. Determining the cells that maintain human prostate adenocarcinoma and the signaling pathways characterizing these tumor-propagating cells is critical for developing effective therapeutic strategies against this population".

Cancer Commons's insight:

Stoyanova T, Cooper AR, Drake JM, Liuc X et al.

PNAS, Nov 27, 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Interleukin-30 expression in prostate cancer and its draining lymph nodes correlates with advanced grade and stage

"We provide the first evidence that IL-30 is implicated in PCa progression since I) its expression by PCa or T- and LN-ILK correlates with advanced disease grade and stage, and II) IL-30 exerts pro-tumor activity in hPCa cells"

Cancer Commons's insight:

Di Meo S, Airoldi I, Sorrentino C, Zorzoli A et al.

Clinical Cancer Resrarch, Nov 26, 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

N-acetyl-L-aspartyl-L-glutamate peptidase-like 2 is overexpressed in cancer and promotes a pro-migratory and pro-metastatic phenotype

Cancer Commons's insight:

N-acetyl-L-aspartyl-L-glutamate peptidase-like 2 (NAALADL2) is a member of the glutamate carboxypeptidase II family, best characterized by prostate-specific membrane antigen (PSMA/NAALAD1). In prostate cancer, NAALADL2 expression was associated with stage and Grade, as well as circulating mRNA levels of the NAALADL2 gene. Overexpression of NAALADL2 was shown to predict poor survival following radical prostatectomy.


Whitaker HC, Shiong LL,  Kay JD, Gronberg A et al

Oncogene, Nov 18, 2013

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

HDAC Inhibitor Confers Radiosensitivity to Prostate Stem-Like Cells

"Background: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction. Methods: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrinhi/CD133+), transit-amplifying (TA, α2β1integrinhi/CD133−) and committed basal (CB, α2β1integrinlo) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. Results: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. Interpretation: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction."

 

Cancer Commons's insight:

Frame FM, Pellacani D, Collins AT, Simms MS, et al. British Journal of Cancer. Nov 12, 2013.

more...
No comment yet.
Rescooped by Cancer Commons from Lung Cancer Research Digest
Scoop.it!

Genome-wide Consequences of Deleting Any Single Gene

"Loss or duplication of chromosome segments can lead to further genomic changes associated with cancer. However, it is not known whether only a select subset of genes is responsible for driving further changes. To determine whether perturbation of any given gene in a genome suffices to drive subsequent genetic changes, we analyzed the yeast knockout collection for secondary mutations of functional consequence. Unlike wild-type, most gene knockout strains were found to have one additional mutant gene affecting nutrient responses and/or heat-stress-induced cell death. Moreover, independent knockouts of the same gene often evolved mutations in the same secondary gene. Genome sequencing identified acquired mutations in several human tumor suppressor homologs. Thus, mutation of any single gene may cause a genomic imbalance, with consequences sufficient to drive adaptive genetic changes. This complicates genetic analyses but is a logical consequence of losing a functional unit originally acquired under pressure during evolution."

Cancer Commons's insight:

Teng X, Dayhoff-Brannigan M, Cheng WC, Gilbert CE, et al. Molecular Cell. Nov 7, 2013.

more...
Cancer Commons's curator insight, November 14, 2013 1:32 PM

Teng X, Dayhoff-Brannigan M, Cheng WC, Gilbert CE, et al. Molecular Cell. Nov 7, 2013.

Cancer Commons's curator insight, November 14, 2013 1:32 PM

Teng X, Dayhoff-Brannigan M, Cheng WC, Gilbert CE, et al. Molecular Cell. Nov 7, 2013.

Rescooped by Cancer Commons from Melanoma Research Digest
Scoop.it!

Boston Research Institutes, Hospitals Launch Clinical Genomics Center

Boston Research Institutes, Hospitals Launch Clinical Genomics Center | Prostate Cancer Research Digest | Scoop.it

"A quartet of Boston-area research centers including Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston Children's Hospital, and the Broad Institute have teamed to create a new clinical cancer genomics center that will be headquartered at Dana-Farber. Dana-Farber said today that the new Joint Center for Cancer Precision Medicine will harness a wide range of scientific resources and clinical capabilities from the partners to treat cancer patients and feed treatment data into research programs. The multiple capabilities these partners will share and use in the new center include DNA sequencing and other tumor molecular profiling tools, pathology, radiology, surgery, computational interpretation, and tumor modeling systems, they said."

Cancer Commons's insight:

GenomeWeb Daily News | Nov 12, 2013

more...
Cancer Commons's curator insight, November 13, 2013 8:09 PM

GenomeWeb Daily News | Nov 12, 2013

Cancer Commons's curator insight, November 13, 2013 8:10 PM

GenomeWeb Daily News | Nov 12, 2013

Scooped by Cancer Commons
Scoop.it!

Androgen Receptor Signaling Fuels DNA Repair and Radioresistance in Prostate Cancer

"Successful treatment by genotoxic modalities including radiotherapy is commonly hampered by treatment resistance in advanced cancers. Two new studies now reveal that androgen receptor signaling transcriptionally upregulates a large subset of DNA repair genes, thereby enhancing the repair capacity and promoting radioresistance of prostate cancer. These results provide a mechanistic rationale for a combined treatment by ionizing radiation and androgen deprivation therapy."

Cancer Commons's insight:

Bartek J, Mistrik M , Bartkova J. Cancer Discovery. Nov 2013.

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Enrichment of Human Prostate Cancer Cells with Tumor Initiating Properties in Mouse and Zebrafish Xenografts by Differential Adhesion

Enrichment of Human Prostate Cancer Cells with Tumor Initiating Properties in Mouse and Zebrafish Xenografts by Differential Adhesion | Prostate Cancer Research Digest | Scoop.it

"Prostate tumor-initiating cells (TICs) have intrinsic resistance to current therapies. TICs are commonly isolated by cell sorting or dye exclusion, however, isolating TICs from limited primary prostate cancer (PCa) tissues is inherently inefficient. We adapted the collagen adherence feature to develop a combined immunophenotypic and time-of-adherence assay to identify human prostate TICs."

Cancer Commons's insight:

Bansal N, Davis S, Tereshchenko I, Budak-Alpdogan T, et al. The Prostate. Oct 24, 2013.

more...
No comment yet.
Scooped by Cancer Commons
Scoop.it!

Personal History of Prostate Cancer and Increased Risk of Incident Melanoma in the United States

"Purpose: Steroid hormones, particularly androgens, play a major role in prostatic carcinogenesis. Personal history of severe acne, a surrogate for higher androgen activity, has been associated with an increased risk of prostate cancer (PCa), and one recent study indicated that severe teenage acne was a novel risk factor for melanoma. These findings suggest a possible relationship between PCa and risk of melanoma. We prospectively evaluated this association among US men. Methods: A total of 42,372 participants in the Health Professionals’ Follow-Up Study (HPFS; 1986 to 2010) were included. Biennially self-reported PCa diagnosis was confirmed using pathology reports. Diagnosis of melanoma and nonmelanoma skin cancer (NMSC) was self-reported biennially, and diagnosis of melanoma was pathologically confirmed. We sought to confirm the association in 18,603 participants from the Physicians’ Health Study (PHS; 1982 to 1998). Results: We identified 539 melanomas in the HPFS. Personal history of PCa was associated with an increased risk of melanoma (multivariate-adjusted hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54). Although we also detected a marginally increased risk of NMSC associated with PCa (HR, 1.08; 95% CI, 0.995 to 1.16), the difference in the magnitude of the association between melanoma and NMSC was significant (P for heterogeneity = .002). We did not find an altered risk of melanoma associated with personal history of other cancers. The association between PCa and risk of incident melanoma was confirmed in the PHS (HR, 2.17; 95% CI, 1.12 to 4.21). Conclusion: Personal history of PCa is associated with an increased risk of melanoma, which may not be entirely a result of greater medical scrutiny."

Cancer Commons's insight:

Li WQ, Qureshi AA, Ma J, Goldstein AM, et al. Journal of Clinical Oncology. Nov 4, 2013.

more...
Cancer Commons's curator insight, November 5, 2013 1:24 PM

Li WQ, Qureshi AA, Ma J, Goldstein AM, et al. Journal of Clinical Oncology. Nov 4, 2013.

Scooped by Cancer Commons
Scoop.it!

Radium Ra 223 Dichloride Injection: U.S. Food and Drug Administration Drug Approval Summary

"On May 15, 2013, the U.S. Food and Drug Administration approved radium Ra 223 dichloride (Xofigo® Injection, Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either radium Ra 223 dichloride (Ra-223) plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR 0.70 (95% CI: 0.55, 0.88), p = 0.0019]. At the pre-specified interim analysis, the median OS was 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (> 10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (> 10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Radium-223 is the first alpha-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer."

Cancer Commons's insight:

Kluetz PG, Pierce W, Maher VE, Zhang H, et al. Clinical Cancer Research. Nov 4, 2013.

more...
No comment yet.