Featured
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Article |
Targeted therapy in patients with PIK3CA-related overgrowth syndrome
A PI3KCA inhibitor reverses symptoms in a mouse model of PROS/CLOVES syndrome, which results from gain-of-function mutations in PI3KCA, and produces improvements in patients with PROS/CLOVES syndrome.
- Quitterie Venot
- , Thomas Blanc
- & Guillaume Canaud
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Review Article |
The biology and management of non-small cell lung cancer
- Roy S. Herbst
- , Daniel Morgensztern
- & Chris Boshoff
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Outlook |
Genetics: Complex expressions
Epilepsy is one of the most common neurological disorders to affect the human brain. Many genetic aspects of the disease have been identified, but mechanisms remains elusive.
- Charvy Narain
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Letter |
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
Metformin treatment of rats at physiologically relevant doses inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase.
- Anila K. Madiraju
- , Derek M. Erion
- & Gerald I. Shulman
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Outlook |
Drug development: Time for teamwork
In the face of more drug-resistant bugs and fewer new drugs, partnerships promise a resurgence of antibiotics.
- Mike May
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Outlook |
Microbiology: Resistance fighters
Science goes back to nature to decipher and disrupt the mechanisms by which germs evade antibiotics.
- Bill Cannon
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Article |
CCR5 is a receptor for Staphylococcus aureus leukotoxin ED
A Staphylococcus aureus leukotoxin targets cells expressing the chemokine receptor CCR5, a mechanism for the specificity of leukotoxins towards different immune cells.
- Francis Alonzo III
- , Lina Kozhaya
- & Victor J. Torres
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News |
Diuretic drug improves symptoms of autism
Small-scale trial provides hope for treatment of autistic behaviour in children.
- Mo Costandi
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Research Highlights |
Cancer-drug infertility reversed
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Editorial |
Too much to ask
A market-based malaria-control programme may not be perfect, but it deserves to continue.
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News |
MDMA keeps severe stress at bay
Prolonged relief reported from drug-enhanced therapy sessions.
- Arran Frood
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News |
Chelation-therapy heart trial draws fire
Critics not persuaded that metal-snaring treatment works.
- Ewen Callaway
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Outlook |
Treatments: In the waiting room
After years of making do with drugs developed for other conditions, doctors and scientists are eagerly pursuing drugs that target the social symptoms of autism.
- Michael Eisenstein
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Letter |
HIV therapy by a combination of broadly neutralizing antibodies in humanized mice
Passive immunotherapy with a combination of neutralizing monoclonal antibodies is shown to be effective in suppressing HIV replication in a humanized mouse model.
- Florian Klein
- , Ariel Halper-Stromberg
- & Michel C. Nussenzweig
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Letter |
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations
EZH2 is a methyltransferase that is mutated in lymphoma; here a potent small molecule inhibitor of EZH2 is described, which inhibits the proliferation of EZH2 mutant cell lines and growth of EZH2 mutant xenografts in mice, thus providing a potential treatment for EZH2 mutant lymphoma.
- Michael T. McCabe
- , Heidi M. Ott
- & Caretha L. Creasy
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Outlook |
Therapeutics: Strength in numbers
Several new drugs for treating chronic obstructive pulmonary disease are about to hit the market, with more in the pipeline.
- Duncan Graham-Rowe
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Letter |
Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes
Inhibition of VEGF-B signalling is shown to limit ectopic fatty-acid accumulation, restore peripheral insulin sensitivity and muscle glucose uptake, and preserve pancreatic islet functionality.
- Carolina E. Hagberg
- , Annika Mehlem
- & Ulf Eriksson
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News |
Generic HIV drugs will widen US treatment net
Upcoming patent expiries stand to make medicines cheaper — although less convenient.
- Amy Maxmen
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News & Views |
Shock and kill
Antiretroviral therapies block HIV replication but they do not eliminate inactive viruses within cells. A clinical trial shows that a drug can revive HIV in patients as a potential first step towards a cure. See Letter p.482
- Steven G. Deeks
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News |
TB drugs chalk up rare win
Combination therapy is just one emerging weapon in the fight against tuberculosis.
- Amy Maxmen
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Letter |
Heterodimeric JAK–STAT activation as a mechanism of persistence to JAK2 inhibitor therapy
Chronic exposure to JAK2 inhibitors leads to reactivation of downstream signalling through the formation of heterodimers between JAK2 and other JAK kinases in myeloproliferative neoplasms, which can be overcome with Hsp90 inhibitors.
- Priya Koppikar
- , Neha Bhagwat
- & Ross L. Levine
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News |
Wary approval for drug to prevent HIV
US regulators seek to mitigate risks of combined pill.
- Amy Maxmen
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News |
Mapping identifies best targets for malaria prevention
Seasonal treatment would save lives, but leave many behind.
- Amy Maxmen
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Letter |
Immune self-reactivity triggered by drug-modified HLA-peptide repertoire
The paper describes the mechanism by which small-molecule drugs such as abacavir affect antigen presentation and consequently T-cell response in immunologically based drug reactions such as abacavir hypersensitivity syndrome (AHS) and carbamazepine-induced Stevens–Johnson syndrome (SJS).
- Patricia T. Illing
- , Julian P. Vivian
- & James McCluskey
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Article |
ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner
ZNRF3 and RNF43 are identified as negative feedback regulators of Wnt signalling; the stem-cell growth factor R-spondin is shown to potentiate Wnt signalling by inhibiting ZNRF3.
- Huai-Xiang Hao
- , Yang Xie
- & Feng Cong
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Outlook |
Drugs: An injection of hope
For decades, drugs have barely managed to slow the progression of multiple sclerosis. Therapies are now emerging that may even help to reverse the disease — but are they worth the risk?
- Duncan Graham-Rowe
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News |
LSD helps to treat alcoholism
Retrospective analysis shows hallucinogenic drug helped problem drinkers.
- Arran Frood
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News |
Drug brings HIV out of hiding
Exposing the latent virus to the immune system may be first step to an elusive cure.
- Erika Check Hayden
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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
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Letter |
Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR
Inhibition of activated BRAF has been ineffective in colon cancers with the mutation; here, this is shown to be due to the feedback activation of the epidermal growth factor receptor (EGFR) in response to BRAF inhibition.
- Anirudh Prahallad
- , Chong Sun
- & René Bernards
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News |
High-dose opiates could crack chronic pain
Powerful analgesics can restore normal nerve function.
- Arran Frood
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Research Highlights |
Spoilers of chemotherapy
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Research Highlights |
Double radiation shield
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Research Highlights |
Liver disease target
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Outlook |
Perspective: Acting on the evidence
Allergy isn't the whole story on atopic eczema, says Hywel Williams.
- Hywel Williams
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Editorial |
The mind’s tangled web
Efforts to elucidate how genes and the environment shape the development of autism, although making progress, still fall far short of their goal.
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News Q&A |
Treatment is prevention
Drug treatment for HIV infection is effective in preventing its spread, but implementing this fully will require more resources, says leading NIH scientist.
- Erika Check Hayden
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Comment |
Stigma impedes AIDS prevention
Medical advances cannot help those who deny they are at risk of HIV and avoid HIV tests. Salim S. Abdool Karim describes how such attitudes may be overcome.
- Salim S. Abdool Karim
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News |
AIDS mortality drops in China
Antiretroviral programme marks dramatic success, but report shows what still needs to be done.
- David Cyranoski
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Letter |
BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR–ABL1 kinase inhibition
- Cihangir Duy
- , Christian Hurtz
- & Markus Müschen
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Outlook |
Perspective: The big C — for Chemoprevention
Drugs to prevent cancer are clearly possible despite some early missteps, says Michael B. Sporn. Restoring the cooperative ethos of decades past will help get us there.
- Michael B. Sporn
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News |
Mutations block lung-cancer treatment
Revealing the genetic changes that let tumours escape drugs offers hope for combination therapies.
- Heidi Ledford
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Outlook |
Chemoprevention: First line of defence
Combinations of drugs are showing some promise as therapeutic agents that stop cancer before it starts.
- Lauren Gravitz
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Article |
A critical role for IGF-II in memory consolidation and enhancement
After learning, memories are strengthened through a process called 'consolidation', which requires new gene and protein expression, rendering new information less vulnerable to disruption. Several transcription factor families are involved in this process, but many of the relevant downstream targets are unknown. Here, IGF-II, a protein typically implicated in somatic tissue growth and repair, is identified as an essential factor in memory retention. IGF-II initiates its own network of signalling cascades that can lead to synaptic potentiation and are most effective within a short time frame immediately after learning. Thus, IGF-II represents an endogenous target for potentially modulating cognitive enhancement.
- Dillon Y. Chen
- , Sarah A. Stern
- & Cristina M. Alberini
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News & Views |
Drugs that prevent HIV infection
Two human trials investigate the efficacy of a type of antiretroviral drug — usually used to treat HIV-infected individuals — in preventing HIV infection. The results are heartening.
- Mark A. Wainberg
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News |
High hopes for arthritis drugs
Race is on to develop treatments that inhibit signalling proteins.
- Heidi Ledford
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News |
Motor disorder could have stress-fighting solution
Research reveals possible cause and potential therapy for Parkinson's disease.
- Janelle Weaver
Mapping human microbiome drug metabolism by gut bacteria and their genes
Algeria to tackle HIV/AIDS
Cells of origin in cancer