Cancer Clinical Trials Optimization and Pharmacogenomics

A critical overview of recent clinical trials in cancer is presented focused on signaling pathways blockers or inhibitors with a view to developing successful clinical trials employing personalized cancer therapies. Rational, pharmacogenomic strategies in cancer trials should be adopted that include specific molecular targeting based on adequate data for, and detailed modeling of, cancer cell genomes, modifications of cancer signaling pathways and epigenetic mechanisms. Novel translational oncogenomics research is rapidly expanding through the application of highly sensitive and specific advanced technology, research findings and computational tools and complex models to both pharmaceutical and clinical problems. Multiple sample analyses from several recent clinical studies have shown that gene expression data for cancer cells can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general,'personalized medicine' that will have to be validated through optimally designed clinical trials in cancer. A Human Cancer Genomes and Epigenetics Project is proposed that can provide the essential data required for the optimal design of clinical trials with the goal of achieving significant improvements of the survival rates of cancer patients participating in clinical trials for advanced cancer stages. The results of such a six-year Human Cancer Genomes and Epigenetics Project should also greatly aid with the accelerated, rational development of effective anti-cancer medicines and the chemoprevention of cancers

Predicting Pancreatic Cancer Using Support Vector Machine

This report presents an approach to predict pancreatic cancer using Support Vector Machine Classification algorithm. The research objective of this project it to predict pancreatic cancer on just genomic, just clinical and combination of genomic and clinical data. We have used real genomic data having 22,763 samples and 154 features per sample. We have also created Synthetic Clinical data having 400 samples and 7 features per sample in order to predict accuracy of just clinical data. To validate the hypothesis, we have combined synthetic clinical data with subset of features from real genomic data. In our results, we observed that prediction accuracy, precision, recall with just genomic data is 80.77%, 20%, 4%. Prediction accuracy, precision, recall with just synthetic clinical data is 93.33%, 95%, 30%. While prediction accuracy, precision, recall for combination of real genomic and synthetic clinical data is 90.83%, 10%, 5%. The combination of real genomic and synthetic clinical data decreased the accuracy since the genomic data is weakly correlated. Thus we conclude that the combination of genomic and clinical data does not improve pancreatic cancer prediction accuracy. A dataset with more significant genomic features might help to predict pancreatic cancer more accurately

Translational Oncogenomics and Human Cancer Interactome Networks

An overview of translational, human oncogenomics, transcriptomics and cancer interactomic networks is presented together with basic concepts and potential, new applications to Oncology and Integrative Cancer Biology. Novel translational oncogenomics research is rapidly expanding through the application of advanced technology, research findings and computational tools/models to both pharmaceutical and clinical problems. A self-contained presentation is adopted that covers both fundamental concepts and the most recent biomedical, as well as clinical, applications. Sample analyses in recent clinical studies have shown that gene expression data can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general, ‘personalized medicine’. Several cancer detection techniques are currently under development both in the direction of improved detection sensitivity and increased time resolution of cellular events, with the limits of single molecule detection and picosecond time resolution already reached. The urgency for the complete mapping of a human cancer interactome with the help of such novel, high-efficiency / low-cost and ultra-sensitive techniques is also pointed out

Representativeness of breast cancer cases in an integrated health care delivery system.

BackgroundIntegrated health care delivery systems, with their comprehensive and integrated electronic medical records (EMR), are well-poised to conduct research that leverages the detailed clinical data within the EMRs. However, information regarding the representativeness of these clinical populations is limited, and thus the generalizability of research findings is uncertain.MethodsUsing data from the population-based California Cancer Registry, we compared age-adjusted distributions of patient and neighborhood characteristics for three groups of breast cancer patients: 1) those diagnosed within Kaiser Permanente Northern California (KPNC), 2) non-KPNC patients from NCI-designated cancer centers, and 3) those from all other hospitals.ResultsKPNC patients represented 32 % (N = 36,109); cancer center patients represented 7 % (N = 7805); and all other hospitals represented 61 % (N = 68,330) of the total breast cancer patients from this geographic area during 1996-2009. Compared with cases from all other hospitals, KPNC had slightly fewer non-Hispanic Whites (70.6 % versus 74.4 %) but more Blacks (8.1 % versus 5.0 %), slightly more patients in the 50-69 age range and fewer in the younger and older age groups, a slightly lower proportion of in situ but higher proportion of stage I disease (41.6 % versus 38.9 %), were slightly less likely to reside in the lowest (4.2 % versus 6.5 %) and highest (36.2 % versus 39.0 %) socioeconomic status neighborhoods, and more likely to live in suburban metropolitan areas and neighborhoods with more racial/ethnic minorities. Cancer center patients differed substantially from patients from KPNC and all other hospitals on all characteristics assessed. All differences were statistically significant (p < .001).ConclusionsAlthough much of clinical research discoveries are based in academic medical centers, patients from large, integrated medical centers are likely more representative of the underlying population, providing support for the generalizability of cancer research based on electronic data from these centers

Rethinking the therapeutic misconception: social justice, patient advocacy, and cancer clinical trial recruitment in the US safety net.

BackgroundApproximately 20% of adult cancer patients are eligible to participate in a clinical trial, but only 2.5-9% do so. Accrual is even less for minority and medically underserved populations. As a result, critical life-saving treatments and quality of life services developed from research studies may not address their needs. This study questions the utility of the bioethical concern with therapeutic misconception (TM), a misconception that occurs when research subjects fail to distinguish between clinical research and ordinary treatment, and therefore attribute therapeutic intent to research procedures in the safety net setting. This paper provides ethnographic insight into the ways in which research is discussed and related to standard treatment.MethodsIn the course of two years of ethnographic fieldwork in a safety net hospital, I conducted clinic observations (n=150 clinic days) and in-depth in-person qualitative interviews with patients (n=37) and providers (n=15). I used standard qualitative methods to organize and code resulting fieldnote and interview data.ResultsFindings suggest that TM is limited in relevance for the interdisciplinary context of cancer clinical trial recruitment in the safety net setting. Ethnographic data show the value of the discussions that happen prior to the informed consent, those that introduce the idea of participation in research. These preliminary discussions are elemental especially when recruiting underserved and vulnerable patients for clinical trial participation who are often unfamiliar with medical research and how it relates to medical care. Data also highlight the multiple actors involved in research discussions and the ethics of social justice and patient advocacy they mobilize, suggesting that class, inequality, and dependency influence the forms of ethical engagements in public hospital settings.ConclusionOn the ground ethics of social justice and patient advocacy are more relevant than TM as guiding ethical principles in the context of ongoing cancer disparities and efforts to diversify clinical trial participation

Advances in breast cancer treatment and prevention: preclinical studies on aromatase inhibitors and new selective estrogen receptor modulators (SERMs).

Intensive basic and clinical research over the past 20 years has yielded crucial molecular understanding into how estrogen and the estrogen receptor act to regulate breast cancer and has led to the development of more effective, less toxic, and safer hormonal therapy agents for breast cancer management and prevention. Selective potent aromatase inhibitors are now challenging the hitherto gold standard of hormonal therapy, the selective estrogen-receptor modulator tamoxifen. Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer. Two recent studies in preclinical model systems that evaluate mechanisms of action of these new drugs and suggestions about their optimal clinical use are discussed

Polypharmacy in elderly cancer patients : challenges and the way clinical pharmacists can contribute in resource-limited settings

The aim of this study was to address the problems associated with polypharmacy in elderly cancer patients and to highlight the role of pharmacists in such cases in resource‐limited settings. A narrative review of existing literature was performed to summarize the evidence regarding the impact of polypharmacy in elderly cancer patients and the pharmaceutical strategies to manage it. This review emphasizes the significance of polypharmacy, which is often ignored in real clinical practice. Polypharmacy in the elderly cancer population is mainly due to: chemotherapy with one or more neoplastic agents for cancer treatment, treatment for adverse drug reactions due to neoplastic agents, the patient's comorbid conditions, or drug interactions. The role of the clinical pharmacist in specialized oncology hospitals or oncology departments of tertiary care hospitals is well established; however, this is not the case in many developing countries. A clinical pharmacist can contribute to solving the problems associated with polypharmacy by identifying the risks associated with polypharmacy and its management in resource‐limited settings. As in many developed countries, the involvement of a clinical pharmacist in cancer care for elderly patients may play a vital role in the recognition and management of polypharmacy‐related problems. Further research can be conducted to support this role

Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

Indexación: Web of ScienceTumor angiogenesis is widely recognized as one of the hallmarks of cancer. Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1) upregulation of compensatory/alternative pathways for angiogenesis; (2) vasculogenic mimicry; and (3) vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.http://www.mdpi.com/1422-0067/17/9/148

ASCO 2007: What remains important for breast cancer systemic therapy in the routine setting?

The 43rd ASCO Annual Meeting took place from June 1-5, 2007 at McCormick Place in Chicago, IL, USA. This year's meeting had the special theme of `Translating Research into Practice', particularly featuring 445 abstracts on translational research in addition to approximately 2,000 abstracts presented on subjects like surgery, radiation therapy, chemotherapy, endocrine therapy, and targeted therapies. This short summary will focus on the two important breast cancer oral presentation sessions only, and will try to comment on the presented data with regard to their immediate impact on clinical practice. Many more research results regarding breast cancer were presented (all presentations will be available to the public from September 1, 2007 at wwwasco.org). In general, breast cancer data presented at this year's ASCO Annual Meeting confirmed current standards, and introduced promising new substances which may soon enter clinical practice. The 44th ASCO Annual Meeting will again be held in Chicago from May 30 to June 3, 2008. Those who do not want to wait another year may visit ASCO's first special Breast Cancer Symposium taking place September 7-8, 2007 in San Francisco, CA, USA. Whether this meeting will start a new tradition of a specialized ASCO breast cancer symposium, and how this development will eventually will impact on the regular San Antonio Breast Cancer Symposium in December, only time will tell

Targeted therapy for breast cancer prevention.

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer