New Computer Program Can Help Uncover Hidden Genomic Alterations that Drive Cancers

Cancer is rarely the result of a single mutation in a single gene. Rather, tumors arise from the complex interplay between any number of mutually exclusive abnormal changes in the genome, the combinations of which can be unique to each individual patient. To better characterize the functional context of genomic variations in cancer, researchers at University of California San Diego School of Medicine and the Broad Institute developed a new computer algorithm they call REVEALER.

To continue reading click here: Program to uncover hidden genomic alteration

 

Prolonged lymphocytosis during Ibrutinib therapy

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has outstanding activity in patients with chronic lymphocytic leukemia. Most patients experience lymphocytosis, representing lymphocyte egress from nodal compartments.

This resolves within 8 months in the majority of patients, but a subgroup has lymphocytosis lasting >12 months. Here we report a detailed characterization of patients with persistent lymphocytosis during ibrutinib therapy. Signaling evaluation showed that while BTK is inhibited, downstream mediators of B-cell receptor (BCR) signaling are activated in persistent lymphocytes. These cells cannot be stimulated through the BCR and do not show evidence of target gene activation.

Progression-free survival is not inferior for patients with prolonged lymphocytosis vs those with traditional responses. Thus, prolonged lymphocytosis is common following ibrutinib treatment, likely represents the persistence of a quiescent clone, and does not predict a subgroup of patients likely to relapse early.

For more information: CLICK HERE

Idelalisib and Rituximab in relapsed chronic lymphocytic leukemia.

Patients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with acceptable side-effect profiles are needed for this patient population.

The combination of idelalisib and rituximab, as compared with placebo and rituximab, significantly improved progression-free survival, response rate, and overall survival among patients with relapsed CLL who were less able to undergo chemotherapy. (Funded by Gilead; ClinicalTrials.gov number, NCT01539512.).

For More information about this publication: CLICK HERE

Raising the Bar

Have you seen the new Jacob’s Medical Center building being built just across from the Moores Cancer Center? To read more about the project and the incredible commitment to creating a healthier world, CLICK HERE!

The $839 million facility is part of a multi-billion dollar university investment in the future of health care for the entire region. It will allow UC San Diego Health System to fulfill its potential of becoming one of the country’s premier academic health systems.

Stopping the Spread of Cancer

Stopping cancer’s spread: New protein found to control deadly cancer metastasis

Researchers have found a critical element that may explain why some cancers spread farther and faster than others, a discovery that could lead to one of the Holy Grails of cancer treatment: containing the disease.

Scientists from the University of California, San Diego School of Medicine, Dr. Thomas J. Kipps and colleagues,  have identified a protein that seems to serve as a switch, regulating the spread of cancer from the primary tumor to distant spots in the body – a process known as metastasis.  The protein is used by embryo cells during early development, but then disappears from the body after an individual comes out of the womb.

Read more- Fox News Report: Dr. Kipps

ROR1 Antibody

Ibrutinib, a potential breakthrough in treating chronic lymphocytic leukemia (CLL)

(TIME.com) — It’s called ibrutinib, and it’s a potential breakthrough in treating chronic lymphocytic leukemia (CLL) that could leave patients with fewer side effects than chemotherapy.   

 

Read the story from CNN:  Ibrutinib new hope for CLL Treatment

 

4/6/2013 Fighting Cancer at the UC San Diego Moores Cancer Center

In an article published in the San Diego Union Tribune,  assistant project scientist, Emanuela Ghia, PhD, is highlighted at the Moores UC San Diego Cancer Center fight against cancer in association with the American Cancer Society.  While this article focuses on breast cancer research, it highlights some of the important advances, applications, and techniques that we are applying in our fight against CLL and other blood cancers.

To read the full article click on the link below:

Genetics Seen as Key to Cancer Fight

Dr. Kipps Best Practices in Medicine

Dr. Charles Burton, President Elect of the Association for Medical Ethics, and Dr. Thomas Kipps of UC San Diego engage in a lively discussion on identifying best practices in medicine and developing strategies that reap the benefits of academic-industry collaborations without violating real or perceived conflicts of interest. Burton and Kipps are presented by the Center for Ethics in Science and Technology in San Diego. (#24058)

UCTV Video Presentation

Genetics and Epigentics

By Drs. Ghia and Smith

Chronic Lymphocytic Leukemia (CLL) is a disease that causes uncontrollable growth of body’s white blood cells, called B-lymphocytes or B cells. Patients with aggressive disease experience a rapid increase in white blood cells counts over a relatively short period of time and will require treatment soon after diagnosis. On the other hand, in patients with indolent disease, the rise white blood cell counts occurs more slowly. Unfortunately, indolent forms of CLL invariably transition to aggressive CLL, necessitating treatment. Understanding this transition from indolent to aggressive disease, known as CLL progression, is one Emanuela Ghia, Ph.D.’s primary research interests.

Dr. Ghia, an Assistant Project Scientist in Dr. Thomas Kipps’ laboratory, has been researching the mechanisms that drive the progression of CLL, collaborating with Erin Smith, Ph.D., from the Genome Information Sciences Division, led by Kelly Frazer, Ph.D., at the UC San Diego Moores Cancer Center. More specifically, they are working to identify the genetic and epigenetic changes that drive CLL progression.

What are genetic and epigenetic changes? 

Genetic changes are mutations that occur in DNA. Interestingly, depending on their location and type, some mutations may have no negative consequences on our health while others can facilitate cancer growth. For example, in CLL some mutations may accelerate the growth of B-lymphocytes. Epigenetic changes are due to alterations in what genes are actually expressed. Such control of gene expression allows for different cell types, such your as skin cells or blood cells, to have striking differences in what proteins they use even though both have the same blueprint DNA, which codes for these proteins. An important process that turns on or turns off genes is called “methylation”.

Drs. Ghia and Smith are evaluating leukemia cells from patients who progressed from indolent to aggressive disease and required treatment. Leukemia cells are collected at two time points: (1) within 1 year from diagnosis and (2) after 4 or more years from diagnosis and within 1 year of requiring therapy. The collection of these leukemia cells allow Drs. Ghia and Smith to perform whole-genome sequencing* to study genetic changes and to perform methylation analyses** to study epigenetic changes.

This study is designed to allow researchers in the field of CLL to understand the genetic and epigenetic changes that are the key players driving CLL progression. Moreover, this important study should provide hope for patients with CLL because it will enable the development of new therapies specifically designed to target the genetic and epigenetic changes determined to play an important role in CLL progression.

*Whole-genome sequencing is an efficient method to selectively sequence the coding regions of the genome and also to calculate allele frequency. Exons are short, functionally important sequences of DNA which represent the regions in genes that are translated into protein. In the human genome there are about 180,000 exons: these constitute about 1% of the human genome, which translates to about 30 megabases (Mb) in length.

**DNA methylation array is designed to interrogate whether known DNA CpG islands are methylated or not. CpG islands are genomic regions that contain a high frequency of cytosine and guanine next to each other. DNA methylation is one of several epigenetic mechanisms that cells use to control gene expression.

Drs. Ghia and Smith are working with the UC San Diego’s Moores Cancer Center “My Answer to Cancer” Program**. This initiative is working to pinpoint the root cause of several cancers, ranging from chronic lymphocytic leukemia to breast.

The UC San Diego Moores Cancer Center is poised to implement genomic sequencing and personalized care for all of our patients and transform the way we treat cancer. Sharing space with researchers and clinical trials means that the Moores Cancer Center can quickly deliver new discoveries from the laboratory to our patients. Simply put, UC San Diego Moores Cancer Center is the perfect place for the MY ANSWER TO CANCER initiative. Please visit “My Answer to Cancer” at http://cancer.ucsd.edu/mac/ to learn more about this initiative.