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Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment

Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment | Cancer Biology Research Digest | Scoop.it

Vemurafenib, a selective RAF inhibitor, extends survival among patients with BRAF V600E–mutant melanoma. Vemurafenib inhibits ERK signaling in BRAF V600E–mutant cells but activates ERK signaling in BRAF wild-type cells. This paradoxical activation of ERK signaling is the mechanistic basis for the development of RAS-mutant squamous-cell skin cancers in patients treated with RAF inhibitors. We report the accelerated growth of a previously unsuspected RAS-mutant leukemia in a patient with melanoma who was receiving vemurafenib. Exposure to vemurafenib induced hyperactivation of ERK signaling and proliferation of the leukemic cell population, an effect that was reversed on drug withdrawal.

 

November 7, 2012DOI: 10.1056/NEJMoa1208958

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Cancer Commons's curator insight, February 1, 2013 11:45 AM

Callahan, M, Rampal, R ... Levine, RL, Chapman, PB. NEJM. Dec. 13, 2013.

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Facing Cancer, a Stark Choice

Facing Cancer, a Stark Choice | Cancer Biology Research Digest | Scoop.it
Double mastectomies are on the rise, both among women with cancer in only one breast and those with a genetic risk.
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Hard-to-Treat Myc-Driven Cancers May Be Susceptible to Drug Already Used in Clinic

Drugs that are used in the clinic to treat some forms of breast and kidney cancer and that work by inhibiting the signaling molecule mTORC1 might have utility in treating some of the more than 15 percent of human cancers driven by alterations in the Myc gene, according to data from a preclinical study published inCancer Discovery, a journal of the American Association for Cancer Research.
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Study Suggests Breast Cancer Overdiagnosed

As a result of mammographic screening programs, as many 1.3 million women over age 40 were overdiagnosed with breast cancer over 3 decades, researchers reported. (See video of discussants)

 

This study examined trends from 1976 through 2008 in the incidence of early-stage breast cancer (ductal carcinoma in situ and localized disease) and late-stage breast cancer (regional and distant disease) among women 40 years of age or older.


The investigators interpret the data to suggest that there is substantial overdiagnosis, accounting for nearly a third of all newly diagnosed breast cancers, and that screening is having, at best, only a small effect on the rate of death from breast cancer.

 

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Multivitamins in the Prevention of Cancer in Men The Physicians' Health Study II Randomized Controlled Trial

Multivitamins in the Prevention of Cancer in Men The Physicians' Health Study II Randomized Controlled Trial | Cancer Biology Research Digest | Scoop.it

In this large-scale randomized trial of 14 641 middle-aged and older men, a daily multivitamin supplement significantly but modestly reduced the risk of total cancer during a mean of 11 years of treatment and follow-up. Although the main reason to take multivitamins is to prevent nutritional deficiency, these data provide support for the potential use of multivitamin supplements in the prevention of cancer in middle-aged and older men.


JAMA. 2012;():1-10. doi:10.1001/jama.2012.14641.

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Any Screening for Colon Cancer Better Than None (CME/CE)

(MedPage Today) -- Alternatives to screening colonoscopy demonstrated similar accuracy for detecting colorectal cancer at a lower cost in people who have an initial negative colonoscopy, according to a computer simulation of screening strategies.
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Molecular ‘portraits’ of tumours match patients with trials in everyday clinical practice

Researchers in France are taking advantage of the progress in genetic and molecular profiling to analyse the make-up of individual cancer patients’ tumours and, using this information, assign them to particular treatments and phase I clinical...
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Stem cell scientists discover potential way to expand cells for use with patients

Stem cell researchers have discovered a new "master control gene" for human blood stem cells and found that manipulating its levels could potentially create a way to expand these cells for clinical use.
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Study finds firefighters face increased cancer risk

A new effort is launched to educate firefighters about the threat they face from cancer.youtube.com...
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Possible therapy identified for tamoxifen-resistant breast cancer

Possible therapy identified for tamoxifen-resistant breast cancer | Cancer Biology Research Digest | Scoop.it

Possible therapy identified for tamoxifen-resistant breast cancer. Researchers have discovered how tamoxifen-resistant breast cancer cells grow and proliferate.

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Cancer trials can lack clear information on biopsies

Cancer trials can lack clear information on biopsies | Cancer Biology Research Digest | Scoop.it

Cancer trials can lack clear information on biopsies. People participating in cancer drug trials aren't always given the most straightforward explanation of possible risks and benefits from invasive procedures that may be involved, according...

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Statins Protect the Heart During Breast Chemo (CME/CE)

(MedPage Today) -- Women being treated for breast cancer with anthracycline chemotherapy experienced less cardiotoxicity if they also were receiving statins, researchers found.
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AHA: HF Tied to Higher Risk for Fatal Cancer

LOS ANGELES (MedPage Today) -- Patients who developed heart failure had a 68% increased risk of cancer, which was associated with a 56% increased risk of death, researchers reported here.
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DNA deletions promote cancer, collateral damage makes it vulnerable

DNA deletions promote cancer, collateral damage makes it vulnerable | Cancer Biology Research Digest | Scoop.it
Working with cell lines of glioblastoma multiforme, the most lethal type of brain tumor, researchers from the Dana-Farber Cancer Institute at Harvard Medical School, and some now at The University of Texas MD Anderson ...
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Replication stress links structural and numerical can... [Nature. 2013] - PubMed - NCBI

PubMed comprises more than 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity. CIN is observed in most solid tumours and is associated with both poor prognosis and drug resistance. Understanding a mechanistic basis for CIN is therefore paramount. Here we find evidence for impaired replication fork progression and increased DNA replication stress in CIN+ colorectal cancer (CRC) cells relative to CIN- CRC cells, with structural chromosome abnormalities precipitating chromosome missegregation in mitosis. We identify three new CIN-suppressor genes (PIGN (also known as MCD4), MEX3C (RKHD2) and ZNF516 (KIAA0222)) encoded on chromosome 18q that are subject to frequent copy number loss in CIN+ CRC. Chromosome 18q loss was temporally associated with aneuploidy onset at the adenoma-carcinoma transition. CIN-suppressor gene silencing leads to DNA replication stress, structural chromosome abnormalities and chromosome missegregation. Supplementing cells with nucleosides, to alleviate replication-associated damage, reduces the frequency of chromosome segregation errors after CIN-suppressor gene silencing, and attenuates segregation errors and DNA damage in CIN+ cells. These data implicate a central role for replication stress in the generation of structural and numerical CIN, which may inform new therapeutic approaches to limit intratumour heterogeneity.

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Workshop on access to clinical-trial data and transparency kicks off process towards proactive publication of data

 

“The European Medicines Agency is committed to proactive publication of clinical-trial data, once the marketing-authorisation process has ended. We are not here to decide if we publish clinical-trial data, but how.” This is how Guido Rasi, Executive Director of the Agency, opened the workshop on access to clinical-trial data and transparency held on 22 November 2012.

 

This event marks the first step in the process to proactive publication of clinical-trial data, a decision the Agency made earlier this year. This decision aims to build trust and confidence in the system by allowing re-analysis of clinical-trial data by stakeholders.

 

The Agency is aware that there are practical issues and other considerations that need to be addressed and resolved. The workshop allowed the Agency to gather the views, interests and concerns from a broad range of institutions, groups and individuals.

 

Based on these discussions, Hans-Georg Eichler, Senior Medical Officer at the Agency, presented the next step of the process. The Agency will establish policies in close dialogue with its stakeholders in five different areas identified during the workshop. These are:

protecting patient confidentiality; clinical-trial-data formats; rules of engagement; good analysis practice; legal aspects.

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Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment

Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment | Cancer Biology Research Digest | Scoop.it

Vemurafenib, a selective RAF inhibitor, extends survival among patients with BRAF V600E–mutant melanoma. Vemurafenib inhibits ERK signaling in BRAF V600E–mutant cells but activates ERK signaling in BRAF wild-type cells. This paradoxical activation of ERK signaling is the mechanistic basis for the development of RAS-mutant squamous-cell skin cancers in patients treated with RAF inhibitors. We report the accelerated growth of a previously unsuspected RAS-mutant leukemia in a patient with melanoma who was receiving vemurafenib. Exposure to vemurafenib induced hyperactivation of ERK signaling and proliferation of the leukemic cell population, an effect that was reversed on drug withdrawal.

 

November 7, 2012DOI: 10.1056/NEJMoa1208958

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Cancer Commons's curator insight, February 1, 2013 11:45 AM

Callahan, M, Rampal, R ... Levine, RL, Chapman, PB. NEJM. Dec. 13, 2013.

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Statins Linked to Lower Cancer Mortality (CME/CE)

(MedPage Today) -- Statin use is associated with a lower risk of dying from cancer for people who used the cholesterol-lowering drugs before their cancer diagnosis, researchers reported.
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Melanoma Drug Triggers Mutant Leukemia (CME/CE)

(MedPage Today) -- A patient with BRAF-positive melanoma had proliferation of leukemic cells associated with activation of a signaling pathway by treatment with a BRAF inhibitor, authors of a case study reported.
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Ovarian cancer patients have lower mortality rates when treated at high-volume hospitals

Women who have surgery for ovarian cancer at high-volume hospitals have superior outcomes than similar patients at low-volume hospitals, new research suggests.
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Mesothelioma drug slows disease progression in patients with an inactive NF2 gene

Preliminary findings from the first trial of a new drug for patients with mesothelioma show that it has some success in preventing the spread of the deadly disease in patients lacking an active tumour suppressor gene called NF2.
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Sanofi Halves Price of Cancer Drug Zaltrap After Sloan-Kettering Rejection

Sanofi Halves Price of Cancer Drug Zaltrap After Sloan-Kettering Rejection | Cancer Biology Research Digest | Scoop.it
Sanofi Halves Price of Cancer Drug Zaltrap After Sloan-Kettering RejectionNew York TimesIn an unusual move, a big drug company said on Thursday that it would effectively cut in half the price of a new cancer drug after a leading cancer center said...
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'Controversial' acupuncture study for women battling cancer sparks debate

'Controversial' acupuncture study for women battling cancer sparks debate | Cancer Biology Research Digest | Scoop.it
Mancunian Matters'Controversial' acupuncture study for women battling cancer sparks debate ...Mancunian MattersThe three-year study, led by the University of Manchester, last week revealed that patients suffering from mental and physical exhaustion...
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Study: Statins Appear to Improve Cancer Survival - The Atlantic

Study: Statins Appear to Improve Cancer Survival - The Atlantic | Cancer Biology Research Digest | Scoop.it
The AtlanticStudy: Statins Appear to Improve Cancer SurvivalThe AtlanticPROBLEM: Statins -- like the brand names Lipitor, Zocor, and Crestor -- are the most commonly prescribed medications for lowering cholesterol.
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New mechanism of action for PARP inhibitors discovered

New understanding of how drugs called PARP inhibitors, which have already shown promise for the treatment of women with familial breast and ovarian cancers linked to BRCA mutations, exert their anticancer effects has led to the identification of...
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Brain cancer therapy that kills tumor cells with an adenovirus heads for Phase 2 trial

Brain cancer therapy that kills tumor cells with an adenovirus heads for Phase 2 trial | Cancer Biology Research Digest | Scoop.it
Brain cancer treatment is also the target of several medical device companies including NovoCure, which had its noninvasive device approved last year for glioblastoma multiforme, and Monteris Medical, which developed a ...
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