Monday, January 17, 2011
Teacher – Learner Contract Gynecologic Surgery Block
Note: question #5 - page 3 (exam while patient under anesthesia)
Cancer Epigenetics - 2010 - CA (includes discussions Lynch Syndrome etc...)
"The term “epigenetics” refers to variability in gene expression, heritable through mitosis and potentially meiosis, without any underlying modification in the actual genetic sequence."
No Gene-Environment Interactions Found in Million Women Study of Breast Cancer 2010 - CA: A Cancer Journal for Clinicians - Wiley Online Library
".....Regarding the question of gene-environment
interactions, lead author Ruth Travis, MD, PhD, adds that “Results from
this study suggest that common genetic and environmental factors
(reproductive and lifestyle factors) act independently on breast cancer
risk, so regardless of common inherited genetic variation, a woman can
still reduce her risk by modifying her lifestyle, for example by
maintaining a healthy body weight and limiting alcohol intake.”
The
absence of interactions means that priorities for risk-reducing
strategies are similar for most women (for example, being based on known
risks associated with lifestyle and reproductive factors) regardless of
the common genetic risk factors for the disease, she says. Dr. Travis
is an epidemiologist, research fellow, and senior scientist in the
cancer epidemiology unit at Oxford University....."
full free access: Poly(ADP-Ribose) polymerase (PARP) inhibitors: Exploiting a synthetic lethal strategy in the clinic - A Cancer Journal for Clinicians - Wiley Online Library
see also:
Table 1. DNA Repair Pathways
(Lynch Syndrome, BRCA 1/2, FANC, ATM, MYH ;
Table 2. PARP Inhibitor Clinical Trials; Other Potential Synthetic Lethal Strategies for PARP Inhibitors.....
Conclusions:
"The synthetic lethal targeting of DNA repair pathways, as exemplified by PARP inhibitors, in cancers bearing HR DNA repair defects is showing considerable potential for delivering selective tumor cell kill while sparing normal cells, and offers a scientifically rational and potentially broad clinical application in oncology.64 Several challenges related to the development of these inhibitors remain, including the identification of robust predictive biomarkers of HR deficiency in cancers. The dissection of the underlying mechanisms of PARP inhibitor resistance and establishment of optimal drug combinations and strategies for chemoprophylaxis with these therapies remain high priorities. It is important to be aware that different PARP inhibitors may have varying potencies on individual members of the PARP superfamily and also affect other targets, resulting in distinct toxicity and efficacy profiles. In the future, it is envisioned that this tumor-specific synthetic lethal strategy with PARP inhibitors may potentially be utilized against cancers with similar molecular defects but diverse anatomical origins.118 Such a paradigm shift in drug discovery may crucially bring us closer to our ultimate goal of personalized medicine."
free full access - Cancer screening in the United States, 2011 - CA: A Cancer Journal for Clinicians - Wiley Online Library
Cancer Screening in the United States, 2011
A Review of Current American Cancer Society Guidelines and Issues in
Cancer Screening
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