Chemotalk Newsletter

Chemotalk Newsletter, Vol. 99 July 1, 2016

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Hi, Everyone.  This story isn't new, but many people missed it first time around.  It's worth repeating:


Mutations Increase Breast Cancer Risk

By Nicholas Bakalar

Mutations in a gene called PALB2 raise the risk of BREAST CANCER in women by almost as much as mutations in BRCA1 and BRCA2, the infamous genes implicated in most inherited cases of the disease.

Previous data had indicated that mutations in PALB2 were linked to breast cancer, and many genetic tests already screen for them.  But it had not been clear to what extent these mutations raised a carrier's odds of developing the disease.

Dr. Marc Tischkowitz, an associate professor of medical genetics at the University of Cambridge, and his colleagues studied 362 members of 154 families with the PALB2 mutations.  None had BrCA1 or BRCA2 mutations, but all had at least one family member with breast cancer and a mutation in PALB2.  There were 311 women with the PALb2 mutations, of whom 229 had breast cancer, and 51 men with the mutation, of whom seven had the disease.

The results were published in The New England Journal of Medicine.

Over all, the researchers found, a PALB2 mutation carrier had a 355 chance of developing cancer by age 70.  By comparison, women with bRCA1 mutations have a 50% to 70% chance of developing breast cancer by that age, and those with BRCA2 have a 40% to 60% chance.

The lifetime risk for breast cancer in the general population is about 125.

The breast cancer risk for women younger than 40 with PALB2 mutation was eight to nine times as high as that of the general population.  The risk was 6 to 8 time as high among women older than 60.

The scientists were not able to explain why younger women with the mutations were at higher risk.  And there were too few men, Dr. Tischkowitz said, to make a judgment about their risk.

The data also indicated that women with the PALB2 mutations were slightly more likely to have "triple negative" breast cancer -- a form resistant to hormone treatment, more aggressive, and more likely to recur than other subtypes.

Dr. Aness B. Chagpar, the director of the breast cancer at Yale-New Haven Hospital, who was not involved in the work, said she was impressed with the study but cautioned that other factors must be considered in evaluating a woman's risk.

"This has to be tailored to the patients, who may have other mutations and varying family risk," she said.  "With no family history, the increase they found is 35%.  If you have two or more family members with cancer they found a risk of 58%."

The study used data from 14 sites in eight countries but found no significant geographic variations in the prevalence.  The researchers write that larger studies are needed to detect such differences, as well as to assess the role of lifestyle and hormone use on breast cancer risk in PALB2 mutation carriers.  Breast cancer risk depends not just on genes, but how they interact with the environment.

Official guidelines do not recommend screening for breast cancer genes in most women, only for those with a family history of the disease.  Dr. Tischkowitz said that such women should consider testing for PALB2 mutations if they are negative for BRCA1 and BRCA2 mutations.

Dr. Chagpar said: "As the testing becomes more common, we'll hopefully end up with studies with thousands of patients in them.  We're going to start getting answers to hard questions."

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A team of researchers elaborated a computational method to track the progress of the COLORECTAL CANCER. It is a scientific advance that can bring new perspectives to discover the factors that push this pathology and the selection of efficient therapies.

In this new international study, published in the journal Proceedings of the National Academy of Sciences (PNAS), there is the participation of the experts Víctor Moreno, from the Faculty of Medicine and Health Sciences of the University of Barcelona, the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO), and Rebeca Sanz-Pamplona (IDIBELL-ICO), among other researchers.

What conditions provoke "tumour growth"?

Colon cancer has a similar frequency in both men and women, whereas rectal cancer is more common among men. Globally, cases of this cancer are around a 1.4M per year and 700.000 deaths. In Spain, there are 32.000 new cases per year and 14.000 deaths, while in Catalonia around 13.000 men and 14.000 women are living with a diagnose of colorectal cancer.

According to Professor Víctor Moreno, from the Department of Clinical Sciences of the UB "like in most tumours, the colorectal is characterized by big chromosomal alterations (deletion, amplification) and specific mutations. These factors regarding the DNA create important alterations in the RNA and the metabolism of the tumour cells". Professor Giulio Caravagna, from the University of Edinburgh, says that the research "proposes a bioinformatics protocol to detect uncommon regularities in the origins and course of the tumour". This protocol could be a key progress to understand a disease which is characterized by a "low number of common genome alterations in different patients", says the expert. Bud Mishra, researcher of the New York University, added that "the model helps us to predict how the tumour genome will change over time".

Traditionally, it was thought that cancer was begun with a rebel cell, and it spread due to a combination of cell-autonomous genetic interactions: mutations in oncogenes, with the potential ability to cause the cancer, and the failure of the tumour suppressor genes that controlled it. However, the techniques of advanced sequencing have made a more complex profile of the cancer progression. In a more specific way, everything points to the interaction between cells in a tumour population to be more relevant than what it was before, since tumours are more heterogeneous in cells than what it was thought.

PiCnIc: a new tool to track cancer progression

The scientific team got these interactions with a model that allows creating the cell image of the colorectal cancer propagation. That is why they developed a modelling system -Pipeline for Cancer Inference, or PiCnIc- which uses genetic sequencing data to predict the causes.

PiCnIc considers the function of the driver mutations, which boost cancer progression, apart from other factors such as alteration in number of copies (deletions and amplifications) and the tandem influence and alterations on drivers. To test the viability of the models, the scientific team has compared the predictions to the available knowledge on the growth dynamics of colorectal cancer. With their results, they prove that PiCnIc is a useful tool to reflect on the knowledge of biomedical research on the disease progression. "This new methodology is innovative because it involves a probability model which infers the order of the events (mutations and alteration in number of copies)", says Professor Víctor Moreno.

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This could be really important!


Report Will Provide a Comprehensive View of the US Cancer Research for the National Cancer Moonshot Initiative,

Elsevier, a world-leading provider of scientific, technical and medical information products and services, today announced an initiative with the White House National Cancer Moonshot Task Force to develop a comprehensive study of CANCER research in the United States.

The Elsevier report will provide a road map of the cancer research landscape to identify pockets of expertise and opportunity and will be made available for free. It is intended to equip the leaders of the National Cancer Moonshot Initiative and other public and private interests with the data and analytics necessary to make informed decisions about research investments that will accelerate cancer activities while mitigating some of the investment risk and achieve a decade's worth of advances in five years.

The announcement of Elsevier's benchmark report came on the eve of a national conference on cancer research in Washington, D.C., hosted by U.S. Vice President Joe Biden. The event will bring together scientists, oncologists, donors and patients. Dubbed the "National Cancer Moonshot Summit," the daylong conference on Wednesday, June 29, at Howard University, is intended to galvanize Biden's final-year push to double the pace of research toward curing cancer. The Cancer Moonshot Summit, aimed at creating action and fostering collaborations around the goals of the Cancer Moonshot, will be the very first time that stakeholders representing all types of cancers will convene under one national charge.

"Cancer is a large, diverse and consistently expanding disease. There have been significant breakthroughs, but cancer itself is continually evolving which makes it extremely challenging to assess where the opportunities and challenges lie," said Dr. Brad Fenwick, Elsevier's Senior Vice President for Global Alliances and project lead. "The first critical step on any journey is to know where you are. For the National Cancer Moonshot Initiative, we'll be providing an outline of the current state of cancer research relative to the areas of focus, as well as impact derived from the large data sets and research collaborations. Ultimately the report will provide a pathway to the most promising outcomes that will affect the greatest number of people."

To help the National Cancer Moonshot Initiative achieve its goals, Elsevier proposed to work with the White House Task Force to conduct this first-ever, data-driven analysis around the central theme of collaboration and identify what works well and what areas prove to be more challenging. Elsevier will underwrite the study, and will use a citation-based approach to identify interdisciplinary research, as well as measure the frequency and value of interdisciplinary collaborations to identify centers of expertise by institution as well as geographically. This will ensure the report fully captures the dynamics of a research landscape in which subjects are constantly emerging and changing. Dr. Fenwick expects the report to be completed by Fall 2016.

Elsevier's study of cancer research will be one of a series of reports developed by Elsevier in the past year that includes stem cell research, brain science, sustainability science and other topics. These reports are used by funding bodies, policy makers, and research organizations to evaluate current progress and chart future actions through informed decisions about needed policies and investments.

About Elsevier: 

Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions - among them ScienceDirect, Scopus, Elsevier Research Intelligence and ClinicalKey - and publishes over 2,500 journals, including The Lancet and Cell, and more than 35,000 book titles, including a number of iconic reference works.

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See you next month...


And if you have any thoughts of how this newsletter could be improved, please email me directly, at

Elaine Jesmer

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