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Showing 151 - 200Will mTOR Inhibitors Change the Treatment of Endocrine-sensitive HER2-negative Breast Cancer?
For the treatment of endocrine-sensitive metastatic breast cancer, the combination of an mTOR inhibitor and an endocrine agent represents a promising new option. At the 2012 Breast Cancer Symposium, the 18-month update of BOLERO-2, which tested therapy with everolimus (Afinitor) plus exemestane,...
Mutational Activation of PI3K-AKT Pathway and Change in HER2 Expression in Trastuzumab-resistant Breast Cancer
Insensitivity of HER2-amplified breast cancer to trastuzumab (Herceptin) has been associated with both changes in HER2 expression and activation of the PI3K-AKT pathway in laboratory studies. Chandarlapaty and colleagues from Memorial- Sloan Kettering Cancer Center in New York and Fox Chase Cancer...
Effects of LKB1 Mutation and mTOR Inhibition on IGFR1 Pathway in NSCLC
LKB1 is a serine/threonine kinase that has been found to be mutated in approximately 20% to 30% of patients with non–small cell lung cancer (NSCLC). LKB1 acts as a tumor suppressor by activating AMPK, and loss of LKB1 by point mutation or deletion suppresses AMPK, leading to increased mTOR...
Revised Everolimus Dosing and New Safety/Efficacy Data for Approval in Subependymal Giant Cell Astrocytoma
On August 29, 2012, everolimus in a tablet for oral suspension form (Afinitor Disperz) was given accelerated approval for the treatment of pediatric and adult patients with tuberous sclerosis complex who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but...
Effects of LKB1 Mutation and mTOR Inhibition on IGFR1 Pathway in Non-small Cell Lung Cancer
LKB1 is a serine/threonine kinase that has been found to be mutated in approximately 20% to 30% of patients with non–small cell lung cancer (NSCLC). LKB1 acts as a tumor suppressor by activating AMPK, and loss of LKB1 by point mutation or deletion suppresses AMPK, leading to increased mTOR...
French Investigators Prospectively Test Genomically Driven Treatment in Metastatic Breast Cancer
Whole-genome DNA analysis prospectively identified alterations in metastatic tumors that could be individually targeted with molecular agents, in a study presented at the 2012 European Society for Medical Oncology (ESMO) Congress by Fabrice André, MD, of Institut Gustave-Roussy, Villejuif, France....
BRAF Mutations in Colorectal Cancer: The Next Frontier
Some 5% to 10% of patients with colorectal cancer harbor the BRAF mutation, placing them at risk for poor treatment response and worse outcomes. The ASCO Post interviewed S. Gail Eckhardt, MD, an expert in this area who is Professor and Head of the Division of Medical Oncology at the University of...
Smoking Linked to Shorter Disease-free Survival in Stage III Colon Cancer
According to an analysis reported by Amanda Phipps, PhD, MPH, Assistant Professor of Epidemiology at the University of Washington and Assistant Member at Fred Hutchinson Cancer Research Center, Seattle, and colleagues in the Journal of Clinical Oncology, patients with stage III colon cancer who...
Progression of Renal Cell Carcinoma Linked to Shifts in Tumor Metabolism
Investigators in The Cancer Genome Atlas (TCGA) Research Network have uncovered a connection between how tumor cells use energy from metabolic processes and the aggressiveness of the most common form of kidney cancer, clear cell renal cell carcinoma. Their findings demonstrate that normal...
Learning to Negotiate the Genomic Complexities of Cancer
The Cancer Genome Atlas (TCGA) Research Network recently reported the results of an integrated analysis of the genomic features of 373 endometrial carcinomas.1 This report joins previously published results of similar analyses in ovarian, breast, and colorectal cancers, squamous cell carcinoma of...
Integrated Genomic Characterization of Endometrial Carcinomas Suggests New Classification Scheme
As recently reported in Nature, investigators in The Cancer Genome Atlas Research Network performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas, including 307 endometrioid and 66 serous or mixed histology cases, using array- and...
Outcomes with Adjuvant Trastuzumab in HER2-positive Breast Cancer Not Affected by PTEN Status
PTEN is a negative regulator of PI3K/AKT signaling. PI3K/AKT signaling can be activated by HER2, and it has been hypothesized that alteration in this pathway may affect sensitivity to trastuzumab (Herceptin). Preclinical data and some of the limited available clinical data suggest that loss or...
Targeted Suppression of a Reactivated Developmental Pathway in Hepatocellular Cancer
This issue of The ASCO Post summarizes the results of an important study recently published in The New England Journal of Medicine by Yong and colleagues. As outlined, investigators from the National University of Singapore Yong Loo Lin School of Medicine have identified re-expression of SALL4 as a ...
Oncofetal Protein SALL4 Is a Marker of Aggressive Hepatocellular Carcinoma and a Potential Therapeutic Target
Hepatocellular carcinomas with characteristics of embryonic stem cell and progenitor cell gene expression are associated with particularly poor prognosis. SALL4 is an oncofetal protein that is expressed in the human fetal liver and normally silenced in the adult liver, but re-expressed in a...
Nodal Metastases More Likely if Tumors Have Breast Cancer Stem and Progenitor Cells With PI3K/Akt Signaling Defects
Patients with breast tumors in which breast cancer stem and progenitor cells have a genetic abnormality of the PI3K/Akt signaling pathway are more likely to have lymph node metastases, according to a study in JAMA Surgery. “These oncogenic defects may be missed by gross molecular testing of the...
Prognostic Significance of MTOR Pathway Component Expression in Neuroendocrine Tumors
The MTOR serine/threonine kinase pathway is implicated in regulation of neuroendocrine tumor growth. In a study reported in the Journal of Clinical Oncology, Qian and colleagues investigated the potential prognostic significance of MTOR pathway component expression in patients with neuroendocrine...
Focal Adhesion Kinase Regulates YB-1–Mediated Paclitaxel Resistance in Ovarian Cancer
It has been found that focal adhesion kinase (FAK) inhibition sensitizes ovarian cancer to the effects of taxanes. In a study reported in the Journal of the National Cancer Institute, Kang and colleagues evaluated the response of taxane-resistant and taxane-sensitive ovarian cancer models to a...
Common Mutations May Impact Neoadjuvant Treatment Outcomes in Breast Cancer
Emerging research is suggesting that outcomes from neoadjuvant chemotherapy may be correlated with two genetic mutations that are common in breast cancer—PIK3CA and TP53. Their presence may affect response to treatment, and mutational shift after treatment may affect survival, according to studies...
More Support for ‘All-RAS’ Testing in Metastatic Colorectal Cancer
Multiple studies reported at the 2014 Gastrointestinal Cancers Symposium add further support for widening the genetic analysis of colorectal cancer tumors. In fact, experts predict that more extensive genetic testing for RAS gene mutations (in KRAS and NRAS) beyond the routine analysis of KRAS exon ...
Targeting Cancer Stem Cells in Breast Cancer: A Potential Clinical Strategy
Preclinical models have suggested that cancer stem cells play a role in tumor recurrence and metastasis following adjuvant therapy, and Max S. Wicha, MD, and his research team are deciphering the mechanisms by which this might happen. A true understanding of cancer stem cells will have important...
Promising Compounds in Development for Multiple Myeloma
The term “novel agents” has been used for the past decade to describe proteasome inhibitors and immunomodulatory drugs that are now conventionally used for multiple myeloma. However, even newer agents in development will be considered truly novel when they hit the market, as they represent new...
NCCN Clinical Practice Guidelines in Oncology: 2014 Updates
At the 19th Annual Conference of the National Comprehensive Cancer Network (NCCN), held recently in Hollywood, Florida, NCCN Panel members presented updates for several tumor types, briefly summarized here. For a more complete description of all updates, visit www.nccn.org. Breast Cancer Guidelines ...
Ongoing Clinical Trials Actively Recruiting Patients With Pancreatic Cancer
The information in this Clinical Trials Resource Guide includes details of actively recruiting clinical studies of patients with pancreatic cancer. All of the studies are listed on the National Institutes of Health website at ClinicalTrials.gov. The studies presented here are nonrandomized,...
Ongoing Clinical Trials Actively Recruiting Children With Cancer
The information in this Clinical Trials Resource Guide includes actively recruiting clinical studies of children with cancer. The studies include pilot and phase I and II studies evaluating new therapies, functional imaging tests, tests to measure the neuropsychological and behavioral function in...
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....
Tackling the Heterogeneity of Triple-Negative Breast Cancer
Triple-negative breast cancer is now recognized as a very complex subtype for which one treatment will not be applicable to all, according to Mohammad Jahanzeb, MD, Professor of Clinical Medicine at the University of Miami and Director of the UM Sylvester Deerfield Campus, who gave an update on...
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 ...
Targeting KRAS Mutations in Lung Cancer: No Longer Impossible
The KRAS mutation has long been considered “undruggable,” but new approaches in drug development may change this. The end result could be effective new treatment options for KRAS-mutated non–small cell lung cancer (NSCLC), according to David R. Gandara, MD, who described the emerging findings at...
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...
Ongoing Clinical Trials Actively Recruiting Patients With Intraocular Cancer
The information contained in this Clinical Trials Resource Guide includes actively recruiting clinical studies of children and adults with intraocular cancers. The studies include pilot, phase 0, phase I, phase II, and observational trials evaluating new combination therapies, vaccines, optical...
Clinical Trials Actively Recruiting Patients With Breast Cancer
The information contained in this Clinical Trials Resource Guide includes actively recruiting clinical studies for people with breast cancer. The studies include phase I and II, interventional, and observational trials evaluating new therapies; diagnostic tools; genetic counseling; the association ...
Novel Agents May Address Endocrine Therapy Resistance
Progress has recently been swift in the development of new drugs to improve the response to hormone therapy in breast cancer, according to Hope S. Rugo, MD, Professor of Medicine and Director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco, Helen...
Potential Roles for Metformin and Everolimus in Obese Women With ER-Positive Breast Cancer
Obesity increases the risk of breast cancer death in postmenopausal women with estrogen receptor (ER)-positive breast cancer, although underlying mechanisms remain unclear. In studies reported in the Journal of the National Cancer Institute, Fuentes-Mattei and colleagues identified an association...
Clinical Trials Actively Recruiting Patients With Colon or Rectal Cancer
The information contained in this Clinical Trials Resource Guide includes actively recruiting clinical studies of people with colon or rectal cancer in the newly diagnosed and metastatic settings. The studies include phase I, Ib, II, observational, and interventional trials investigating new drug...
New Agents and Novel Targets for Multiple Myeloma
New therapies for multiple myeloma have dramatically improved life expectancy, but despite these advances, 5-year overall survival still remains below 50%. Investigators are in hot pursuit of new therapies that will extend remissions and improve survival. Thus far, monoclonal antibodies,...
Capsaicin
Scientific name: 8-methyl-N-vanillyl-6-nonenamide Brand names: Zostrix cream 0.025% or 0.075%, Salonpas Gel-Patch Hot, Sinus Buster (homeopathic intranasal spray). The use of dietary supplements by patients with cancer has increased significantly over the past 20 years despite insufficient evidence ...
The Basket Trial: An Evolving Clinical Trial Design
The recently published results of the CUSTOM (Molecular Profiling and Targeted Therapies in Advanced Thoracic Malignancies) trial, reviewed in this issue of The ASCO Post, describe a basket trial focused on identifying molecular biomarkers in advanced non–small cell lung cancer (NSCLC), small...
Outcomes of the CUSTOM ‘Basket’ Trial of Molecular Profiling and Targeted Therapy in Advanced Thoracic Malignancies
In the phase II CUSTOM trial reported in the Journal of Clinical Oncology, Ariel Lopez-Chavez, MD, Anish Thomas, MD, and colleagues performed molecular profiling of tumors in patients with advanced non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), or thymic malignancies and...
Emerging Technology Will Help Tackle Tumor Complexity
Emerging laboratory technology will be “moving the bar forward” in terms of molecular markers, genomics, and gene-expression profiling, with the potential for huge payoffs to oncologists and patients, according to Mark Pegram, MD, the Susy Yuan-Huey Hung Professor of Medicine at Stanford School of...
Primary vs Metastatic Breast Cancer: The Genetic Landscape Varies
Breast tumors that recur appear to have a different genetic profile than those that do not, and they often demonstrate targetable mutations, according to the largest study of genetic sequencing of breast cancer tissue to date.1 This finding was presented at the 2015 European Cancer Congress. “We...
Actionable Targets Identified in Brain Metastases
New research shows that paired primary tumor and brain metastases share a common ancestor, but as the metastases develop in the brain, they exhibit novel genetic alterations that can activate a number of signaling pathways. More than half of the mutations represent potential therapeutic targets....
RAB35 Protein Implicated in Oncogenic Process in the PI3K/AKT Pathway
A protein known to play a role in transporting the molecular contents of normal cells into and out of various intracellular compartments can also turn such cells cancerous by stimulating a key growth-control pathway. By conducting a large-scale search for regulators of the signaling pathway known...
Sequencing Studies Show High Frequency of Actionable MET Mutations in Pulmonary Sarcomatoid Carcinoma
In a study reported in the Journal of Clinical Oncology by Liu et al, next-generation sequencing revealed a high frequency of actionable MET mutations in patients with pulmonary sarcomatoid carcinoma. Study Details In the study, whole-exome sequencing was used in a discovery set of 10 patients...
Protein Imbalance in Akt Pathway May Trigger Cancer
Cancer can be caused solely by protein imbalance within cells, a study of ovarian cancer has found. Until now, genetic aberrations have been seen as the main cause of almost all cancer. The research, published by Timsah et al in Oncogene, demonstrates that protein imbalance is a powerful prognostic ...
Phase II Trial Shows Activity of mTOR Inhibitor Ridaforolimus in Advanced Endometrial Carcinoma
In a randomized phase II trial reported in the Journal of Clinical Oncology, Oza et al found that the mTOR inhibitor ridaforolimus was active in previously treated advanced endometrial carcinoma. Study Details In the open-label study, 130 patients with progressive disease after one or two lines...
ASCO 2015: Biomarker Analysis Reveals Several Potential Treatment Targets in Subtype of Anal Cancer
Squamous cell anal carcinomas are rare, representing only about 2% of gastrointestinal cancer diagnoses. These cancers, which are associated with the human papillomavirus (HPV), sometimes prove very difficult to treat, recurring or developing metastases following standard treatment. Seeking to...
AACR 2015: New PARP Inhibitor Combination Shows Early Promise for a Wide Range of Cancer Patients
A combination of two molecularly targeted drugs, olaparib (Lynparza) and the investigational agent AZD5363, was safe and yielded responses in patients with a variety of cancer types, including breast, ovarian, and prostate cancers, regardless of BRCA1/2-mutation status, according to data from the...
Outcomes of Phase II Basket Trial of Molecular Profiling and Targeted Therapy in Advanced Thoracic Malignancies
In a basket trial (CUSTOM) reported in the Journal of Clinical Oncology, Lopez-Chavez et al performed molecular profiling of tumors in patients with advanced non–small cell lung cancer (NSCLC), small cell lung cancer, or thymic malignancies and assigned those in any of five actionable...
Phase II Study Shows Activity of Everolimus and Letrozole in Recurrent Endometrial Carcinoma
Interaction of the estrogen receptor and PI3K/AKT/mTOR pathways and the finding of resistance to hormonal therapy mediated by PI3K activation suggest a benefit of adding an mTOR inhibitor to hormonal treatment in endometrial carcinoma. In a phase II study reported in the Journal of Clinical...
Study Identifies Signaling Pathway Responsible for Generating Slowly Proliferating, Chemoresistant Cancer Cells
Although scientists know that all cancers contain a mixture of both rapidly and slowly proliferating cancer cells, which complicates the detection and treatment of patients with cancer and may cause disease relapse long after apparently curative treatment, the circumstances and molecular details of ...
