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Showing 801 - 850From Ireland to America and Back, Patrick G. Johnston, MD, PhD, Thrives on Bringing Research Findings to Clinical Practice
Patrick G. Johnston, MD, PhD, FMedSci, Professor of Oncology and President and Vice-Chancellor of Queen’s University Belfast, grew up in Derry, a city in Northern Ireland. Derry is distinct in being Ireland’s only remaining fully intact walled city, considered one of the finest examples of a walled ...
The Road to Progress in Lung Cancer Treatment
Despite promising new agents and therapeutic approaches, 5-year lung cancer survival rates have lagged far behind those of most other malignancies. To shed light on some of the important issues facing lung cancer experts, The ASCO Post recently spoke with internationally recognized lung cancer...
What Do Humans and Laboratory Rats Have in Common?
The requirements for sound evidence of a drug’s therapeutic benefit have translated laboratory experience to human testing. In the laboratory, experimental animals give their lives to lethal testing of drugs and scientific analysis. LD50, the terminology denoting an anticipated 50% death rate of...
Centrosome Amplification Promotes Cellular Invasion in Mammary Epithelial Cells
Centrosomes, the primary microtubule organizing centers within cells, are commonly amplified in tumors, but the role of centrosome amplification in tumorigenesis is unclear. Centrosome amplification is not favored in nontransformed cells, with extra centrosomes being spontaneously lost in the...
IGF-2/IGF-1R Inhibition Shows Promise in Esophageal Cancer
In a study reported in Clinical Cancer Research, Li and colleagues found that overexpression of Id1 protein resulted in insulin-like growth factor (IGF)-2 production, which, in turn, resulted in esophageal cancer cell proliferation, survival, and invasion via autocrine activation of AKT....
Plasma Tumor DNA Detectable Before and After Surgery in Patients with Early-Stage Breast Cancer
Detecting circulating plasma tumor DNA in patients with early-stage cancer has the potential to influence selection of adjuvant systemic therapy. In a study reported in Clinical Cancer Research, Beaver and colleagues found that plasma tumor DNA could be detected both before and after surgery in...
Melanoma Metastases Exhibit Site-Specific Antigen Heterogeneity Correlating With T-Cell Infiltration
In a study reported in Clinical Cancer Research, Bartlett and colleagues found that melanoma metastases exhibit site-specific antigen heterogeneity that correlates with T-cell infiltration. A total of 3,086 metastatic tumors involving various anatomic sites were assessed for a panel of melanocyte...
Mutations in IGF Pathway Genes Associated With Prostate Cancer Mortality
In a study reported in the Journal of the National Cancer Institute, Cao and colleagues identified mutations in insulin-like growth factor (IGF) pathway genes that were significantly associated with mortality in prostate cancer. Analysis of 530 single nucleotide polymorphisms (SNPs) in 26 IGF...
Mesenchymal Stem Cells With Oncolytic HSV Variants Promising in Glioblastoma Multiforme
Although oncolytic herpes simplex virus (HSV) has been found to be safe in clinical trials in malignant glioblastoma multiforme, its efficacy is limited by insufficient viral spread after tumor resection. In a study reported in the Journal of the National Cancer Institute, Duebgen and colleagues...
FBXW7 as Tumor Suppressor and NOTCH1 Inhibition as Potential Strategy in Melanoma
In a study reported in the Journal of the National Cancer Institute, Aydin and colleagues found that mutation in and inactivation of FBXW7 and accumulation of NOTCH1, a substrate of FBXW7, were associated with melanoma tumorigenesis. FBXW7 was found to be mutated in 8% of 103 melanoma patients, and ...
Prolyl Hydroxylase Inhibition Protects Against Gastrointestinal Radiation Toxicity
In a study reported in Science Translational Medicine, Taniguchi and colleagues found that inhibition of prolyl hydroxylase by genetic knockout or inhibition of all prolyl hydroxylase domain isoforms by the small-molecule dimethyloxallyl glycine (DMOG) resulted in promotion of protection against...
BRCA2 Inhibits Genome Instability by Preventing R-Loop Accumulation
Genome instability and DNA damage in cancer can be induced by mutations in genes involved in pre-mRNA splicing and biogenesis and export of messenger ribonucleoprotein (mRNP). Instability can be mediated by R-loops formed by DNA-RNA hybrids and displaced single-stranded DNA. The TREX-2 complex is...
Spleen Tyrosine Kinase Inhibition Has Promise in High-Risk Precursor B-Cell ALL
In a study reported in Science Translational Medicine, Perova and colleagues found that pre–B-cell receptor–independent spleen tyrosine kinase signaling was necessary for leukemic B-cell survival and proliferation in a mouse model. Investigation of samples from pediatric and adult B-cell acute...
FDA Takes Steps to Help Ensure the Reliability of Certain Diagnostic Tests
The U.S. Food and Drug Administration (FDA) recently took important steps to ensure that certain tests used by health-care professionals to help diagnose and treat patients provide accurate, consistent, and reliable results. First, the FDA is issuing a final guidance on the development, review, and ...
Book Excerpt: Family
I've witnessed incredible courage and zest for life among so many patients from so many walks of life—individuals committed to helping others in spite of their own adversity. Forty years ago, when survival for patients with multiple myeloma was a matter of months, I knew that every person I sat...
Getting Results: How Oncologists and Pathologists Can Work Together to Facilitate Molecular Testing
Advances in molecular testing mean that highly specific information can be detailed about the molecular characteristics of a patient’s tumor, as well as indications of potential responsiveness to targeted therapy. But getting those detailed results from the pathologists can be a challenge to many...
College of American Pathologists Publishes Recommendations for Prostate Cancer Active Surveillance
Recommendations from the United States Preventive Services Task Force and randomized trials have drawn attention to overtreatment of localized, low-risk prostate cancer. PSA screening and changing consensus on PSA testing practices are among the many factors that contribute to the overdiagnosis and ...
15-PGDH Expression in Normal Mucosa May Be Biomarker for Aspirin Prevention of Colorectal Cancer
Aspirin use reduces the risk of colorectal cancer at least in part via inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2, COX-2) pathways. Hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide; 15-PGDH, HPGD) is a metabolic antagonist of PTGS2 and is downregulated in...
Small Molecule Induces Catastrophic Vacuolization and Death of Glioblastoma Cells
In a study reported in Cell, Kitambi and colleagues screened patient-derived glioblastoma cells to identify targetable cellular processes gained by these cells that are not necessarily involved in malignancy. They found that a quinine derivative (NSC13316) selectively compromised viability of...
Dysregulated Cell-Cycle Progression and Akt Hyperactivation in Cancer
Akt plays important roles in cell proliferation, survival, and metabolism. Akt hyperactivation contributes to tumorigenesis and is associated with poor prognosis and resistance to chemotherapy and radiotherapy. It is known that activation of Akt results from phosphorylation at S473 and T308, but it ...
Fusion Protein Improves Dendritic Cell Penetration, Raising Prospect of Efficient Cancer Vaccine
Immunotherapy with dendritic cells in combination with cytotoxic chemotherapy may eliminate minimal disease burden by generating cytotoxic T lymphocytes (CTLs). Improving the cytosolic bioavailability of tumor-specific antigens to improve access to HLA class I molecules would result in better...
BET Bromodomain Inhibition Highly Active in Castration-Resistant Prostate Cancer
Progression to castration-resistant prostate cancer after androgen ablation therapy is primarily due to deregulated androgen receptor signaling. Treatment with agents that target such signaling, such as abiraterone (Zytiga) and enzalutamide (Xtandi), has been successful. However, durable response...
Royal Society Presents 2014 Royal Medal to Tony Hunter, PhD, FRS, Salk Professor
Tony Hunter, PhD, FRS, has been awarded the 2014 Royal Medal for Biological Sciences by the Royal Society, an international fellowship of scientists based in the United Kingdom. The award recognizes Dr. Hunter, Director of Salk Institute Cancer Center in San Diego, for his contributions to the...
Gynecologic Cancer Care: Collaboration With Resource-Challenged Ethiopia
Over the past 40 years, largely because of universal Pap screening, cervical cancer deaths have been drastically reduced in the United States and other wealthy industrialized countries. However, cervical cancer is still a leading cause of cancer death among women in resource-challenged areas of the ...
Potential for Therapeutic Autovaccination Against Solid Tumors With Intratumoral Poly-ICLC
In a study reported in Cancer Immunology Research, Salazar and colleagues found a remarkable response to a strategy of sequential intratumoral and intramuscular injections of the stabilized dsRNA viral mimic and pathogen-associated molecular pattern (PAMP) polyinosinic-polycytidylic...
Modification of T Cells to Target CS1 Improves Eradication of Myeloma Cells
CS1 is a cell surface glycoprotein that appears to be highly expressed on myeloma cells and less expressed on normal cells; CS1 overexpression has been found to promote myeloma cell growth and survival by increasing myeloma adhesion to bone marrow stromal cells and increasing myeloma colony...
PD-1 Identifies Patient-Specific CD8-Positive Tumor-Infiltrating Lymphocytes in Melanoma
Adoptive transfer of tumor-infiltrating lymphocytes can mediate regression of metastatic melanoma. However, there are no effective markers to identify and select patient-specific repertoires of tumor-reactive and mutation-specific CD8-positive lymphocytes, limiting the ability to develop strategies ...
LCS6 Genotype Not Associated With KRAS Mutation Status or Outcome in Stage III Colon Cancer
A let-7 microRNA-complementary site (LCS6) polymorphism in the 3’UTR of KRAS has been shown to disrupt let-7 binding and upregulate KRAS expression. As reported in Clinical Cancer Research, Sha and colleagues found that LCS6 genotype was not associated with KRAS mutation status or disease-free...
Remarkable Response to Sorafenib in Advanced Lung Adenocarcinoma and Oncogenic ARAF Mutation
As reported in Journal of Clinical Investigation by Imielinski and colleagues, whole-genome and RNA sequencing of tumor and normal tissue in a patient with advanced lung adenocarcinoma who exhibited a remarkable response to sorafenib (Nexavar) revealed a somatic ARAF S214 mutation expressed at high ...
Overexpression of Sirt7 Is Associated With Tumorigenesis and Poor Prognosis in Colorectal Cancer
Sirt7, a member of the sirutin family, is overexpressed in some cancers. In a study of the potential role of Sirt7 in colorectal cancer reported in Clinical Cancer Research, Yu and colleagues found that increased Sirt7 protein level in colorectal cancer tissue was associated with higher tumor stage ...
Tissue Microenvironment Affects Activity of PTEN in Leukemia
The tumor suppressor PTEN, which is underexpressed in many cancers, dephosphorylates phosphatidylinositol (3,4,5)-triphosphate and thus inhibits activity of phosphatidylinositol 3-kinases involved in growth factor and survival factor signaling through effectors such as Akt and mTOR. As reported in...
Potential Marker for Response to Anti-EGFR Therapy in KRAS Wild-Type Metastatic Colorectal Cancer
As reported in Clinical Cancer Research, Manceau and colleagues attempted to identify microRNAs that can predict response to anti-EGFR therapy in wild-type KRAS metastatic colorectal cancer patients. Initial screening of 1,145 microRNAs in fresh frozen tumor samples from chemotherapy-refractory...
Extracellular Matrix Stiffness Promotes Malignant Progression Via PTEN-Reducing Effect of Micro-RNA
Tissue mechanics are altered in tumor progression, although many of the mechanisms underlying the changes remain unclear. In a study reported in Nature Medicine, Mouw and colleagues found that increased tissue extracellular matrix stiffness modulated microRNA expression to promote tumor progression ...
TRIM44 Amplification in Esophagogastric, Breast Tumors May Be Marker for mTOR Inhibitor Therapy
TRIM44 family overexpression is associated with carcinogenesis, and TRIM44 has been identified as a prognostic gene. In a study reported in Journal of the National Cancer Institute, Ong and colleagues attempted to identify therapeutic strategies for patients with TRIM44 overexpression. Genomic and...
Delivering Cancer Care in Low-Income Countries
In eealthy industrialized nations like the United States, escalating costs of cancer care have put the term “cost-effective care” on the forefront of health-care policy discussions. However, the cost issues we wrestle with in our $3 trillion health-care system are vague abstractions for much of the ...
Immunotherapy Research of James P. Allison, PhD, Has Led to a Paradigm Shift in the Treatment of Cancer
James P. Allison, PhD, has been bucking the status quo since he was a teenager growing up in the small agricultural town of Alice, Texas, in the 1950s and 1960s. He first butted heads with authority figures when he was in high school and learned that his biology class had omitted the teaching of...
PALB2 Study: Researchers and Patients Must 'Pal' for Progress
The recent publication by Antoniou et al on risk of breast cancer in PALB2 carriers,1 reviewed in this issue of The ASCO Post (page 47), is a contribution to the interesting history of the PALB2 gene, and an important milestone in the expansion of hereditary cancer susceptibility testing in the...
Different Transcriptional Responses to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer
In a study reported in Clinical Cancer Research, Patani and colleagues investigated whether distinct transcriptional responses were associated with the reported increased effectiveness of the estrogen receptor (ER) antagonist fulvestrant (Faslodex) over the aromatase inhibitor anastrozole in...
MSH6 Mutations May Influence Temozolomide Resistance in Treatment-Naive Gliomas Independent of MGMT Methylation
Resistance to temozolomide in glioblastoma has been thought to be largely mediated by expression of the DNA repair enzyme MGMT, although there are data suggesting a role for inactivation of MSH6 and other mismatch repair proteins. In a study reported in Clinical Cancer Research, Nguyen and...
Dissemination of Glioblastoma Multiforme Outside Brain Is Common
The finding of extracranial metastases after organ transplantation from glioblastoma multiforme donors raised issues with the notion that disease spread is restricted to the brain. In a study reported in Science Translational Medicine, Müller and colleagues found that hematogenous spread of...
Potential for Improved Effectiveness and Reduced Toxicity of Radiotherapy With Ultrahigh Dose-Rate FLASH Irradiation
Studies in vitro have suggested that sub-millisecond pulses of radiation produce less genomic instability than continuous prolonged irradiation at the same total dose. In a study reported in Science Translational Medicine, Favaudon and colleagues assessed the effects of ultrahigh dose-rate...
CD44 Expression a Marker for Chemotherapy Resistance in Gastric Cancer, Overcome by Hedgehog Inhibition
CD44 is a gastric cancer stem cell marker, and the hedgehog signaling pathway can be dysregulated by cancer stem cells during tumorigenesis. In a study reported in Clinical Cancer Research, Yoon and colleagues found that high CD44 expression was associated with chemotherapy resistance and poorer...
TP53 Mutation Associated With Chromosome 3p Loss in Head and Neck Squamous Cell Carcinoma
In an analysis of molecular and clinical features associated with survival in head and neck squamous cell carcinoma reported in Nature Genetics, Gross and colleagues found that the TP53 mutation is frequently accompanied by loss of chromosome 3p; the combination of these alterations was associated...
Tumor PD-L1 mRNA Expression Associated With Improved Outcome in Breast Cancer
Inhibition of the PD-1/PD-ligand1 (PD-L1) axis has shown considerable therapeutic promise in several cancers. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway, but its measurement has been limited by the lack of standardized immunohistochemical methods and...
Roswell Park Researchers Awarded Nearly $5 Million to Support Research Projects
Several faculty members at Roswell Park Cancer Institute have been awarded nearly $5 million in grant funding from public and private organizations to further their efforts to find new and better ways to detect and treat cancer and improve patients’ quality of life. The 13 awards, including two for ...
On Being A Mentee and the Value of the Conquer Cancer Foundation’s Career Development Award
At the ASCO Annual Meeting in June, the Conquer Cancer Foundation presented the 2014 recipients of prestigious grants and awards, including the Young Investigator Award, Career Development Award, and the Advanced Clinical Research Award in Breast Cancer. In announcing the awards, Charles W. Penley, ...
Life-Threatening Dermatologic Toxicity
A variety of life-threatening dermatologic adverse events may occur in association with cancer drug therapies. Here, we discuss the recognition and management of three types of such toxicities: type I hypersensitivity/anaphylaxis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and drug rash...
How Accurate Is the Pathologic Assessment of the Partial Mastectomy Specimen?
The pathologic evaluation of lumpectomy margins is “fraught with problems and pitfalls,” said Stuart J. Schnitt, MD, Director of Anatomic Pathology at Beth Israel Deaconess Medical Center and Professor of Pathology at Harvard Medical School, Boston, who was part of a multidisciplinary discussion of ...
Polymorphisms and Cetuximab Benefit in Locally Advanced Rectal Cancer
Polymorphisms in FcγR (receptor for the constant region of immunoglobulin G) have been reported to be associated with improved immune-mediated effects of cetuximab (Erbitux) in metastatic colorectal cancer. In a study reported in Clinical Cancer Research, Sclafani and colleagues analyzed the...
Androgen, Estrogen, and Stem Cell Markers Help Predict Recurrence and Survival in Metastatic Prostate Cancer
In a study reported in Clinical Cancer Research, Fujimura and colleagues developed and tested models to predict prostate-specific antigen (PSA) recurrence and cancer-specific survival in patients with treatment-naive prostate cancer and bone metastases using mRNA expression of genes involved in...
