oncologywatch

This year I’m focusing on Tumor Biology and Human Genetics, with close attention to molecular diagnostics.

Lots of abstracts look promising, including these:

CANCER GENETICS
Comen EA, Lautenberger J, McGee K et al. (Memorial Sloan-Kettering Cancer Center, National Cancer Institute.)
Use of genome-wide scan in women with breast cancer to identify common germline variants that may be associated with recurrence.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11049).
Conclusions: "Genome-wide SNP genotyping of women with breast cancer identified two novel loci that may be associated with disease recurrence. Further studies in larger cohorts will be performed to replicate these findings."
Read the ASCO abstract.

Geier LJ, Sheehan M, Elia M et al. (Kansas City Cancer Center.)
The oncologist as genetic consultant: Two-year results in a large community-based practice.
J Clin Oncol 27, 2009 (suppl; abstr e22140)
Conclusions: "This oncologist-centered model proved to be very effective in identifying mutation carriers, particularly among cancer survivors in whom the hereditary syndrome had been previously overlooked. Acceptance of this approach by pts, physicians, and payers has been extremely high. This model should be considered by oncology practices wanting to add GCRA to their service lines."
Read the ASCO abstract.

EPIDEMIOLOGY/MOLECULAR EPIDEMIOLOGY
Cheung WY, Zhai R, Kulke M et al. (University of Toronto, Harvard School of Public Health, Dana-Farber Cancer Institute, Massachusetts General Hospital, Princess Margaret Hospital.)
Epidermal growth factor (EGF) gene polymorphism, gastroesophageal reflux disease (GERD), and esophageal adenocarcinoma (EAC) risk.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11029)
Conclusions: "EGF A61G polymorphism exerts its effect on EAC susceptibility through an interaction with GERD. Performing EGF genotyping for patients with severe or longstanding GERD can help to identify individuals at the greatest risk of EAC."
Read the ASCO abstract.

IMMUNOBIOLOGY
Busse A, Asemissen A, Schmittel A et al. (Charité-CBF, Charité-CBF/CCM.)
Immune self-tuning in renal cell carcinoma patients.
J Clin Oncol 27, 2009 (suppl; abstr e22069)
Conclusions: "RCC caused an immune-suppressive phenotype in PBMC characterized by increased mRNA expression levels of IL10 and TGFβ. Surprisingly, in contrast to IL10, a high TGFβ mRNA expression level was an independent good prognostic factor. Whether this observation can be attributed to recently described immune promoting functions of TGFβ needs to be determined."
Read the ASCO abstract.

MOLECULAR DIAGNOSTICS & STAGING
Tobin D, Bårdsen K, Kauczynska M et al. (Bhagawan Mahavir Jain Hospital; Shrey Hospital Private Ltd; SP Medical College; Dr. Kamakshi Memorial Hospital; Department of Genetics, Radium-Riskhospitalet; Mercy Health Center.
Performance of a blood-based gene-expression test, BCtect, for early breast cancer detection.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11012)
Conclusions: "The blood based gene expression test showed similar diagnostic performance between women with early and late stage BC, and the test was independent of the subject’s BMI and menopausal status suggesting broad applicability of the test and indicating its clinical potential in younger women where mammography is of less value due to dense breast tissue. No correlation with lesion size was seen suggesting the lower limit of detection is below 8mm."
Read the ASCO abstract.

Müller BM, Kronenwett R, Hennig G et al. (Charité Hospital; Siemens Healthcare Diagnostics; University Hospital.)
Quantitative determination of predictive cancer biomarkers in formalin-fixed, paraffin-embedded tissue using a new, fully automated method for RNA isolation.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11032)
Conclusions: "This novel RNA extraction method is a major technical improvement for implementation of reproducible, high-throughput and cost-efficient testing of cancer biomarkers in the clinical routine and in gene-expression research studies using archived FFPE material in molecular labs."
Read the ASCO abstract.

Rosenwald S, Gibori H, Gilad S et al. (Rosetta Genomics; Sheba Medical Center; NYU School of Medicine; Rabin Medical Center.)
Identification of tumor tissue origin by a microRNA-based molecular assay.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11036)
Conclusions: "Previous studies highlighted the tissue-specificity of microRNA expression. We developed this potential into a diagnostic assay that identifies tumor origins with high accuracy. This assay provides an important new tool for diagnosing tumor tissue origin."
Read the ASCO abstract.

Lebanony D, Benjamin H, Gilad S et al. (Rosetta Genomics; NYU School of Medicine; Rabin Medical Center.)
MicroRNA-based assay for differential diagnosis of squamous from non-squamous non-small cell lung carcinoma.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11069)
Conclusions: "MicroRNAs are becoming an important tool for classification of cancers. A diagnostic assay based on the specificity of a single microRNA accurately identifies squamous from non-squamous NSCLC. This assay provides an important new tool for the classification of NSCLC."
Read the ASCO abstract.

Greco FA, Spigel DR, Yardley DA et al. (Sarah Cannon Research Institute; bioTheranostics.)
Unknown primary cancer (UPC): Accuracy of tissue of origin prediction by molecular profiling.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11070)
Conclusions: "RT-PCR performed on FFPE initial diagnostic tissue was accurate in predicting the primary site of origin in 11 of 16 pts with UPC who eventually had their primary site identified clinically. These data provide a direct validation of the reliability of this RT-PCR assay in predicting the primary site in pts with UPC. When used in concert with clinical features and IHC stains, molecular profiling may provide the basis for more successful site-directed therapy for many of these pts. Prospective studies of RT-PCR in UPC are ongoing."
Read the ASCO abstract.

PROGNOSTIC FACTORS
Pachmann K, Camara O, Runnebaum IB et al. (Clinic for Internal Medicine II; University Hospital Friedrich Schiller University.)
Gauging the response of circulating epithelial tumor cells (CETC) and tumor stem cell subpopulations to therapy of early-stage cancer in the individual patient.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11026).
Conclusions: "CETC and subpopulation monitoring provides an invaluable tool for prompt gauging of systemic therapy in early stage solid tumors as a tool for therapy guidance and optimal personalized therapies to improve therapy results and spare unnecessary treatments."
Read the ASCO abstract.

Mook S, Schmidt MK, van de Velde AO et al. (Netherlands Cancer Institute; Comprehensive Cancer Center Amsterdam (IKA); University of Texas.)
Validation of the web-based tool Adjuvant! in 5,381 Dutch breast cancer patients.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11090)
Conclusions: "Adjuvant! accurately predicts 10-year OS for common tumor types in this first large scale European validation study and is of use for adjuvant treatment-decision making."
Read the ASCO abstract.

TUMOR & CELL BIOLOGY
Kalinsky K, Jacks LM, Hedvat C et al. (Memorial Sloan-Kettering Cancer Center).
Use of multiplex mutation genotyping to identify novel and protective mutations in breast cancer.
J Clin Oncol 27:15s, 2009 (suppl; abstr 11004)
Conclusions: "We have recently defined the positive prognostic significance of PIK3CA mutations in breast cancer. RAS mutations are confirmed to occur rarely in breast cancer. The finding of RET mutations in breast cancer is novel. Future tumor biomarker identification directed towards predictive measurement will assist in tailoring therapy to appropriate patient populations."
Read the ASCO abstract.

Tsai C, Chen T, Chang K, Hsiao S. (Taipei Veterans General Hospital; Taipei-Veterans General Hospital.)
Combination effects of gefitinib plus cisplatin in non-small cell lung cancer (NSCLC): Why have phase III trials failed?
J Clin Oncol 27:15s, 2009 (suppl; abstr 11022)
Conclusions: "In NSCLC cells, combination of GC showed antagonistic interaction likely because gefitinib interfered with cisplatin cell entry. Three-drug combination PCG was not better than two-drug combination PC or PG in either EGFR wild type or mutant cells. Clinically, simultaneously combined EGFR TKI with platinum in NSCLC should be avoided regardless of EGFR mutation status."
Read the ASCO abstract.

Kaiser T, Klein G, Solomayer E et al. (Department of Obstetrics and Gynecology; Center for Medical Research.)
Interactions of breast cancer cells with the microenvironment of the human bone marrow.
J Clin Oncol 27, 2009 (suppl; abstr e22097)
Conclusions: "These data indicate that the crosstalk with osteoblasts affects both the adhesive and the migratory ability of BrCa cells favoring the bone colonization process. Furthermore, the presented experimental conditions may provide useful tools to study effects of antiresorptive drugs like bisphosphonates to improve therapeutic strategies for treatment metastatic bone disease."
Read the ASCO abstract.

[OncologyWatch directory of open-access oncology journals.]

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger). This blog is not a source for medical advice.

Technorati tags:
oncology molecular diagnostics

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Lewis MT. Faith, heresy and the cancer stem cell hypothesis. Future Oncol. 2008 Oct;4(5):585-9. PMID: 18922113

Baylor professor Michael Lewis reviews current theory about cancer stem cells, starting from arguments for their existence:

“Arguments for the existence of tumor-initiating ‘cancer stem cells’ are rooted ultimately in cell theory. A central tenet of cell theory states that, other than the first cell, all cells arise from pre-existing cells. Since all cancers are composed of cells, and have, in most cases, been demonstrated to be clonally derived, most cancers must arise from a single, pre-existing cell – a ‘tumor-initiating cell’. The cancer stem cell hypothesis proposes that tumor-initiating ‘cancer stem cells’ arise from cells that either innately possess or acquire the ability to self-renew (reproduce a new tumor-initiating cell) and serve as a precursor cell able to generate all other cell types characteristic of a given tumor. Thus, the term ‘stem cell’ in the ‘cancer stem cell hypothesis’ refers to a defining set of cellular behaviors responsible for tumor formation, and not necessarily to the identity of the cell of origin."

 

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger). This blog is not a source for medical advice.

technorati tags: cancer stem cells

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Price ND, Foltz G, Madan A, et al. Systems biology and cancer stem cells. J Cell Mol Med. 2008 Jan-Feb;12(1):97-110. PMID: 18031300

A comprehensive review of the state of science regarding cancer stem cells (CSCs), a subset of cells found within tumors and hematological malignancies and theorized to be responsible for starting and maintaining cancer. The authors are from the Institute for Systems Biology, the Seattle Neuroscience Institute, and the Department of Chemical and Biomolecular Engineering & Institute for Genomic Biology at the University of Illinois, Urbana-Champaign.

From the conclusion:

"The identification and prospective isolation of CSCs from leukaemia and a number of solid tumours has spawned a new paradigm in cancer research. From the perspective of systems biology – with the goal of predictive, preventive, personalized, and participatory (P4) medicine – we envision increasingly global assessment of CSCs and their microenvironments (niche) at the level of complete transcriptome, proteome and epigenome, using empowering new high-throughput technologies. The resulting gene expression profile signatures of cancer stem cell would serve as more accurate indicatives for cancer diagnosis and prognosis. Emerging proteomic technologies employing MS and protein chip platforms would allow for identification of better cell-surface markers and their interaction with the resident stem cell niche and potential diagnostic markers from both body fluids and tumour tissues. Incorporating these data into biological networks will provide fundament insights into the biology of CSCs and their abilities for renewal and differentiation. These combined efforts will ultimately lead to new therapeutic strategy specifically targeting CSCs for unprecedented personalized cancer therapy."

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger). This blog is not a source for medical advice.

Technorati tags:
oncology cancer systems biology

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Dahl K, Karlsson M, Marits P, et al. Metinel node–the first lymph node draining a metastasis–contains tumor-reactive lymphocytes. Ann Surg Oncol. 2008 May;15(5):1454-63. PMID: 18299934

Researchers in Sweden identify a new clinical entity.

"We located the first draining lymph node or nodes from metastases or local recurrences; we named them ‘metinel nodes.’ Lymphocytes from the metinel nodes proliferated, showed clonal expansion, and produced interferon gamma (via in vitro expansions on stimulation with tumor homogenate) and interleukins, all of which demonstrate the characteristics of tumor-reactive lymphocytes… We demonstrate that it is possible to locate the first lymph nodes draining subcutaneous, lymphatic, and visceral metastases, the so-called metinel nodes. Metinel node–derived lymphocytes may be used to treat disseminated solid cancer, and clinical trials should evaluate the effect of such treatment."

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger).This blog is not a source for medical advice.

Technorati tags:
oncology cancer colorectal cancer melanoma ovarian cancer breast cancer solid tumors

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Kohrt HE, Olshen RA, Bermas HR, et al. New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients. BMC Cancer. 2008 Mar 4;8:66. PMID: 18315887

A multidisciplinary team at Stanford University Medical Center and other Bay Area institutions have developed a new online calculator for determining risk of non-sentinel lymph node metastasis in breast cancer patients with sentinel lymph node metastasis.

The online calculator is intended for patients who have received a sentinel lymph node biopsy without evidence of obvious non-sentinel lymph node metastasis on physical examination. Three tumor characteristics are required: size of tumor, size of sentinel lymph node metastasis, and presence or absence of angiolymphatic invasion status.

From the statement of purpose:

"Knowing the chance of non-sentinel lymph node metastasis allows clinicians and their patients to balance the benefits and risks of additional axillary lymph node surgery for individualized care."

The calculator is available at this url: https://www3-hrpdcc.stanford.edu/nsln-calculator/ 

Technorati tags:
oncology cancer breast cancer

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Polyak K. Breast cancer: origins and evolution. J Clin Invest. 2007 Nov;117(11):3155-63. Review. PMID: 17975657

A thoroughly up-to-date review article by an associate professor at Harvard Medical School who is a rising star in cancer genetics and the molecular basis of breast cancer. Dr. Polyak has a refreshingly clear and direct writing style:

"Despite significant advances in diagnosing and treating breast cancer, several major unresolved clinical and scientific problems remain. These are related to (a) prevention (who needs it and when), (b) diagnosis (we need more specific and sensitive methods), (c) tumor progression and recurrence (what causes it and how to predict it), (d) treatment (who should be treated and how), and (e) therapeutic resistance (how to predict, prevent, and overcome it)."

Technorati tags:
oncology cancer breast cancer

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Ali MM, Vaidya V. Vitamin D and cancer. J Cancer Res Ther. 2007 Oct-Dec;3(4):225-30. Review. PMID: 18270398

A far-ranging essay on the possible role of Vitamin D, acquired primarily through exposure to the sun via the skin, to inhibit tumor development and growth and reduce mortality for certain cancers. From the results and discussion:

"Although sunlight and vitamin D have been positively associated with non-melanoma skin cancer, ecological studies suggest that sunlight may protect against female breast, ovarian, prostate, and colon cancer. The high prevalence of vitamin D deficiency, combined with the discovery of increased risks of certain types of cancer in those who are deficient, suggest that vitamin D deficiency may account for several thousand premature deaths from colon, breast, ovarian, and prostate cancer annually." 

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oncology cancer colorectal cancer breast cancer ovarian cancer prostate cancer

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Elkum N, Dermime S, Ajarim D, et al. Being 40 or younger is an independent risk factor for relapse in operable breast cancer patients: the Saudi Arabia experience. BMC Cancer. 2007 Dec 5;7:222. PMID: 18053234

The open-source journal BMC Cancer published this study, which is interesting not least because young women are increasingly at risk for breast cancer.

From the discussion:

"Patients included in this study illustrate interesting characteristics where 33.2% are young (≤ 40 years) and 66.8% are pre-menopausal. While the median age at presentation is around 63 years in the United States and Western Europe, the median age at presentation in this study is 45 years. The young age of patients in this study is attributed to the overall age distribution in the KSA, where 50% of the population is less than 15 years of age and only 3% are older than 65 years. These patients’ characteristics are in sharp contrast with those reported in the West."

Technorati tags:
oncology cancer breast cancer

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