Outlook |
Featured
-
-
Outlook |
Biochemistry: A radical treatment
Researchers are counting on drugs that activate a master switch for antioxidant genes to protect lung tissue of COPD patients from an onslaught of free radicals.
- Ken Garber
-
Letter |
Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans
Biochemical and structural analysis of the drug transporter P-glycoprotein in Caenorhabditis elegans at a resolution of 3.4 angstroms is used to generate a homology model of the human protein and supports a picture in which P-glycoprotein uses the energy from ATP hydrolysis to expel lipophilic molecules from the inner leaflet of the cell membrane.
- Mi Sun Jin
- , Michael L. Oldham
- & Jue Chen
-
News |
Studies offer ‘panoramic view’ of lung cancer
Three genome-sequencing trials may help to revamp treatments for the world’s most deadly cancer.
- Monya Baker
-
News & Views |
Exploiting collateral damage
Some mutations in tumour cells play no part in causing cancer, but they generate cellular weak spots that may allow tumour cells to be selectively killed by drugs. See Article p.337
- Ben Lehner
- & Solip Park
-
Article |
Passenger deletions generate therapeutic vulnerabilities in cancer
The ‘collateral’ homozygous deletion of essential redundant housekeeping genes in cancer genomes is shown to confer therapeutic vulnerability on cancer cells with the deletion, without affecting genomically intact normal non-cancerous cells, suggesting new therapeutic opportunities.
- Florian L. Muller
- , Simona Colla
- & Ronald A. DePinho
-
Letter |
A restricted cell population propagates glioblastoma growth after chemotherapy
By using a GFP reporter protein expressed selectively in neural stem cells in a mouse model of glioblastoma, a small subset of GFP-positive glioma cells is shown to be responsible for re-growth of tumours after chemotherapy.
- Jian Chen
- , Yanjiao Li
- & Luis F. Parada
-
Research Highlights |
p53 can be cancer's friend, not foe
-
News |
Neighbouring cells help cancers dodge drugs
Proteins in a tumour's microenvironment play a part in drug resistance.
- Jennifer Carpenter
-
Letter |
Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors
The efficacy of kinase inhibitors in treating cancer is limited by drug resistance; here it is shown that most human tumour cells can develop drug resistance through being exposed to one or more receptor tyrosine kinase ligands.
- Timothy R. Wilson
- , Jane Fridlyand
- & Jeff Settleman
-
Letter |
Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion
The secretion of hepatocyte growth factor by stromal cells in the tumour micro-environment can make melanoma resistant to RAF inhibitors, through the activation of the MET signalling pathway, but a combination of RAF and MET inhibitors can overcome this resistance.
- Ravid Straussman
- , Teppei Morikawa
- & Todd R. Golub
-
News & Views |
Pinprick diagnostics
Rare tumour cells with mutations that confer drug resistance can go undetected by standard testing procedures, according to two studies, which show that such mutations can be detected in patients' blood. See Letters p.532 and p.537
- Eduardo Vilar
- & Josep Tabernero
-
Research Highlights |
Melanoma pathway targeted
-
Letter |
The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
This work on colorectal cancer shows that secondary mutations in KRAS that confer resistance to panitumumab, an anti-EGFR monoclonal antibody, are already present when antibody treatment begins; the apparent inevitability of resistance suggests that combinations of drugs targeting at least two different oncogenic pathway will be needed for treatment.
- Luis A. Diaz Jr
- , Richard T. Williams
- & Bert Vogelstein
-
Letter |
Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
Molecular alterations in KRAS are associated with acquired resistance to anti-epidermal growth factor receptor (EGFR) treatment in colorectal cancer; resistant mutations can be identified in the blood of patients, months before clinical evidence of disease progression.
- Sandra Misale
- , Rona Yaeger
- & Alberto Bardelli
-
Article
| Open AccessWhole-genome analysis informs breast cancer response to aromatase inhibition
Whole-genome analysis of oestrogen-receptor-positive tumours in patients treated with aromatase inhibitors show that distinct phenotypes are associated with specific patterns of somatic mutations; however, most recurrent mutations are relatively infrequent so prospective clinical trials will require comprehensive sequencing and large study populations.
- Matthew J. Ellis
- , Li Ding
- & Elaine R. Mardis
-
News |
Antibody alarm call rouses immune response to cancer
Trial drug outperforms earlier efforts to marshall the body’s defences to combat tumours.
- Erika Check Hayden
-
Article |
Chemical genetic discovery of targets and anti-targets for cancer polypharmacology
Using Ret-driven models of multiple endocrine neoplasia, it is shown that optimal kinase inhibition must aim to target an ideal spectrum of tumour-relevant kinases while avoiding ‘anti-targets’ that cause unwanted toxicity.
- Arvin C. Dar
- , Tirtha K. Das
- & Ross L. Cagan
-
Outlook |
Molecular oncology: The positive in the negative
Researchers are delving into triple-negative breast cancer, uncovering potential drug targets for this difficult-to-treat disease.
- Kendall Powell
-
Research Highlights |
Environment of chemo success
-
Career Brief |
UK drug development
Venture-capital funding in the United Kingdom represents a boost for translational research.
-
Letter |
Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia
Internal tandem duplication mutations in FLT3, known to be associated with a poor prognosis in acute myeloid leukaemia, are now shown to be a valid therapeutic target for the disease.
- Catherine C. Smith
- , Qi Wang
- & Neil P. Shah
-
Research Highlights |
Small, cancer-resistant mice
-
Research Highlights |
Tumours yield to pressure relief
-
News & Views |
Limitations of therapies exposed
Certain drugs that are used to treat cancer affect blood-vessel formation in tumours. But it seems that these antiangiogenic drugs can reduce the efficiency of other anticancer agents and increase the tumours' aggressiveness.
- Oriol Casanovas
-
Research Highlights |
Blocking tumour sugar metabolism
-
News & Views |
Clinical trials unite mice and humans
Anticancer 'co-clinical' trials, in which mice carrying known mutations are treated in parallel with patients enrolled in a simultaneous clinical study, could help to improve therapeutic outcome. See Letter p.613
- Leisa Johnson
-
News |
Drug candidates derailed in case of mistaken identity
PARP inhibitor that wasn't highlights widespread flaws in preclinical studies.
- Heidi Ledford
-
News |
Cancer screen yields drug clues
Huge drug survey brings personalized cancer therapy a step closer.
- Heidi Ledford
-
Letter |
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
The Cancer Cell Line Encyclopedia presents the first results from a large-scale screen of some 947 cancer cell lines with 24 anticancer drugs, with the aim of identifying specific genomic alterations and gene expression profiles associated with selective sensitivity or resistance to potential therapeutic agents.
- Jordi Barretina
- , Giordano Caponigro
- & Levi A. Garraway
-
Article |
Systematic identification of genomic markers of drug sensitivity in cancer cells
Human cancer cell lines are screened with drugs, undergoing clinical or preclinical investigation, to determine specific genomic alterations associated with response to therapeutic agents.
- Mathew J. Garnett
- , Elena J. Edelman
- & Cyril H. Benes
-
News |
Mouse 'avatars' could aid pancreatic cancer therapy
Personalized mouse model may lead to tailored treatments for patients.
- Carina Dennis
-
News |
Mice guide human drug trial
Parallel approach to cancer study provides genetic insights.
- Heidi Ledford
-
Letter |
A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response
In parallel with an ongoing human clinical trial, genetically engineered mouse models of lung cancer with different genetic alterations are treated with chemotherapeutic agents; the results have implications for the clinical trial.
- Zhao Chen
- , Katherine Cheng
- & Kwok-Kin Wong
-
News & Views |
Primed for resistance
A drug for treating melanoma is ineffective in colorectal cancers that have the same causative mutation. Studies of how cells adapt to the drug reveal why this is so, and suggest combination therapies that may be more effective. See Letter p.100
- David B. Solit
- & Pasi A. Jänne
-
News |
DNA robot could kill cancer cells
Device identifies target then releases deadly payload.
- Alla Katsnelson
-
News |
Field narrows in hunt for devil tumour genes
Genome sequences of the Tasmanian devil's infectious cancer stir hopes for a vaccine.
- Ewen Callaway
-
News |
Cancer-causing mutations yield their secrets
Changes to metabolism disrupt cells' ability to differentiate.
- Heidi Ledford
-
Research Highlights |
Chemo spans generations
-
News |
Cancer drugs affect mouse genomes for generations
DNA mutations continue to accumulate in offspring of treated mice.
- Heidi Ledford
-
Research Highlights |
Tumour cells lend a hand
-
-
Article
| Open AccessA novel retinoblastoma therapy from genomic and epigenetic analyses
The retinoblastoma genome is shown to be stable, but multiple cancer pathways are identified that are epigenetically deregulated, providing potential new therapeutic targets.
- Jinghui Zhang
- , Claudia A. Benavente
- & Michael A. Dyer
-
Review Article |
Cancer immunotherapy comes of age
An overview of the latest advances in cancer immunotherapy.
- Ira Mellman
- , George Coukos
- & Glenn Dranoff
-
Outlook |
Drugs: More shots on target
Drugs introduced to fight multiple myeloma in the past decade have revolutionized treatment and extended patients' lives. Are the improvements set to continue?
- Adrianne Appel
-
Outlook |
Diagnostics: The early bird
Identifying the patients most likely to progress from a precancerous condition to multiple myeloma could help doctors catch the disease early and stop it taking hold.
- Lauren Gravitz
-
News & Views |
A drug-resistant duo
The efficacy of the anticancer drug vemurafenib, which is used to treat metastatic melanoma, is plagued by acquired resistance. A picture of how such resistance develops is emerging. See Letter p.387
- Hugo Lavoie
- & Marc Therrien
-
Seven Days |
Seven days: 9–15 December 2011
The week in science: boost for gene therapy; EPA reports concern over fracking; and a fresh clue to ancient water on Mars.
-
News |
Targeted treatment tested as potential cancer cure
Trial will deploy genetically targeted therapy early, rather than as last resort.
- Erika Check Hayden
-
Research Highlights |
Fat fuels abdominal cancers