Expert Opinion: The Therapeutic Target Database: an Internet resource for the primary targets of approved, clinical trial and experimental drugs

Note: the full article is pay-per-view ($$$)

".....Increasing numbers of proteins, nucleic acids and other molecular entities have been explored as therapeutic targets.

A challenge in drug discovery is to decide which targets to pursue from an increasing pool of potential targets, given the fact that few innovative targets have made it to the approval list each year.

Knowledge of existing drug targets (both approved and within clinical trials) is highly useful for facilitating target discovery, selection, exploration and tool development. The Therapeutic Target Database (TTD) has been developed and updated to provide information on 358 successful targets, 251 clinical trial targets and 1254 research targets in addition to 1511 approved drugs, 1118 clinical trials drugs and 2331 experimental drugs linked to their primary targets (3257 drugs with available structure data).

This review briefly describes the TTD database and illustrates how its data can be explored for facilitating target and drug searches, the study of the mechanism of multi-target drugs and the development of in silico target discovery tools."

full free access: World Jnl Gastroenterology-Approach to early-onset colorectal cancer: Clinicopathological, familial, molecular and immunohistochemical characteristics

 World Journal of Gastroenterology - link to article    

Keywords (article) : Early onset colorectal cancer, Microsatellite instability, Lynch syndrome, Microsatellite stable colorectal cancer

Technology Review: Fine-tuning Cancer Treatments

Scientists at the Wellcome Trust Sanger Institute and Massachusetts General Hospital will test 400 compounds, including chemotherapy drugs and molecularly targeted treatments, on 1,000 cancer cell lines containing cancer-related genetic mutations in an effort to advance personalized medicine. The findings are expected to help drugmakers design clinical studies that include only patients who are most likely to benefit from experimental cancer drugs.
 
"...While a number of molecularly targeted cancer drugs, such as gleevec and herceptin, are already on the market, the effectiveness of most of these drugs depends on a single genetic mutation or molecular marker in the tumor. Scientists say that incorporating the diversity of cancer genomics in much greater detail will enable more personalized treatment for a broader number of patients...cont'd

abstract/free full pdf access:P redictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies Cancers

"Abstract: Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer."
 ..........
"High grade serous tumors show particular differences in terms of their development, genetic alterations and prognosis. This has led to the classification of ovarian cancer into two types: type 1 tumors, which are low grade and slowly developing (endometrioid, mucinous and low grade serous tumors), and type 2 tumors, which rapidly progress (high grade serous). In addition, the association of biomarker expression with survival varies substantially between subtypes, and can easily be overlooked in whole cohort analyses. Although these data suggest substantial differences between subtypes, until recently ovarian carcinomas were typically approached as a monolithic entity by researchers and clinicians. This practice impeded progress in understanding the biology or improving the management of the less common ovarian carcinoma subtypes. To avoid this effect, each subtype within a cohort should be analyzed individually. Therefore, molecular classifiers of ovarian cancer are of high clinical relevance in the management of these cancer patients...." cont'd

Clinical Significance of Microsatellite Instability in Sporadic Epithelial Ovarian Tumors

Abstract: CONCLUSION: MSI was infrequent in ovarian tumors, including both borderline and malignant tumors. MSI was found to be uncommon in sporadic ovarian tumors, even by using additional MSI markers. The clinical significance of MSI is not strong in patients with sporadic ovarian tumors.

Link to full text (pdf file):

DISCUSSION
....MSI is caused by mutations in the mismatchrepair genes (MMR). MSI has been implicated in the pathogenesis of colon, endometrial, and gastric
carcinomas that occur in the setting of HNPCC (Lynch Syndrome), and also in a subset of sporadic cancers such as upper urinary tract, stomach, colon, andendometrial carcinomas.
In ovarian cancers, the reported incidence of MSI ranges from 0 to 37%, depending on the number and type of markers. Sood et al. first
reported the incidence of MSI in ovarian cancer using the NCI criteria.....Therefore, further study of molecular events that are correlated with ovarian tumors is needed."

MicroRNAs in ovarian carcinomas -- Dahiya and Morin 17 (1): F77 -- Endocrine-Related Cancer

(abstract) FOCUS REVIEW
MicroRNAs in ovarian carcinomas
Neetu Dahiya1 and Patrice J Morin1,2
1 Laboratory of Cellular and Molecular Biology, National Institute on Aging, NIH Biomedical Research Center, 251 Bayview Boulevard, Suite 100, Room 6C228, Baltimore, Maryland 21224, USA
2 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA

Now's the time to find biomarkers on purpose -- Annals of Oncology

"Studies need to be conducted to determine the optimal design for using genome-wide profiling to identify putative biomarkers of drug response. To date, most biomarkers of drug response identified through genome-wide profiling have occurred through retrospective analysis of available tissue. To really progress this field, realistic planning for biomarker discovery and validation in clinical trials needs to be conducted. We, as clinical scientists, need to progress from only using convenient clinical cohorts to identify biomarkers to actually planning and following through with prospective clinical trials whose aims are to discover and/or validate putative biomarkers of drug response. To initiate a study without a realistic plan for discovery and validation reflects a lack of serious desire to find robust clinical predictors.^.... Until this becomes more commonplace, the genomic revolution will be focused on manuscript generation and investigator career development, leaving the benefit to patients nothing more than an unrealized dream."

Molecular Cancer | Full text | Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas