Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Digging Deeper Into Cancer

Published: Tuesday, November 19, 2013
Last Updated: Tuesday, November 19, 2013
Bookmark and Share
What a pathologist looks for in a Pap test sample, but hopes not to find, are oddly shaped cells with abnormally large nuclei. The same is true for prostate and lung cancer biopsies.

“If you just open a text on the pathology of cells, you see hundreds of strange-looking cells – this one with a gigantic nucleus, that one with vacuoles that push the nucleus aside,” says Wallace Marshall, PhD ’97, an associate professor of biochemistry and biophysics. “It’s like an atlas of freakish cells.”

Marshall wondered if this lineup of distorted cells might hold a clue to a new way to fight cancer. Because cancer cells divide so quickly, they’re on a fast track to mutate and develop resistance to chemo drugs. So new drugs are continually added to the mix, often triggering an arms race between the chemo drugs and the cancer – a race that the cancer sometimes wins.

Marshall thought of a different strategy: what if the enlarged nuclei, and specialized cellular structures called organelles, actually drive cancer metabolism? If so, then developing ways to reverse organelle growth could rob cancer cells of the proteins and other resources they need to grow and proliferate.

The hypothesis exemplifies one of UC San Francisco’s precision medicine pillars: basic discovery. The long path to developing potent new treatments often starts with an observation in the lab that then leads to a question about a fundamental life process. This in turn prompts a “testable” hypothesis. Science is full of hypotheses that don’t pan out because experiments fail to support them. But those that survive the rigors of investigation can change minds – and save lives.

Marshall’s lab has begun to study the processes by which organelles enlarge. Once armed with that understanding, his team plans to test drug candidates to “deprogram” them and counter their growth.

Such a treatment approach could circumvent the key vulnerability of chemotherapy, Marshall says. It would not aim directly at the biochemical pathway that allows cancer cells to multiply rapidly – the very capacity that also allows them to mutate and develop resistance to drugs.

Instead, it would attack the cascade of chemical signals that regulates organelle growth. Marshall reasons that these signals are not likely to be the same ones that cancer cells use to mutate and evade the drugs.

Even if cancer cells did develop resistance to drugs targeting their organelle growth, Marshall says, they would have double the work to evade both these drugs and the more conventional ones countering cellular proliferation.

Marshall likens organelles to “reaction vessels” – akin to tanks in a chemical plant, churning out products through chemical reactions. The size and design of the reaction vessels, he says, are just as important as the chemistry going on inside them. Shrink the vessels, and you cut their productivity.

He actually has two hypotheses about the link between organelle size and cancer. One postulates that gargantuan nuclei and organelles derive from the cancer cell’s need to ramp up its metabolism. If the “reaction vessels” could be made to return to their earlier, smaller configuration, the cancer cell might starve.

In his second scenario, the cancer cell’s hypermetabolism is a result of organelle growth, not its cause. But, again, by driving the organelles back to a more normal size range, the cell would revert to a less malignant state.

Marshall stresses that neither scenario has been tested. That’s his long-range goal. To get there, he must first understand the natural mechanisms that regulate organelle growth. His lab is now at the stage of finding out what specific steps control organelle growth – how a cell knows the size of its nuclei and mitochondria, for example, or knows if it’s well fed.

If he can identify the genetic controls or enzymes and other molecules that underlie these processes, he would have targets for potential drugs to reprogram the abnormal growth.

In collaboration with UCSF’s Small Molecule Discovery Center, his lab is carrying out automated, “high-throughput” tests, like those used in commercial drug development, to screen for drug candidates that impede specific genes or molecules. Such screening efforts often search through tens of thousands to hundreds of thousands of compounds to find the few able to block the target enzyme.

His colleague Davide Ruggero, PhD, who holds UCSF’s Helen Diller Family Endowed Chair of Basic Science in Urological Cancer, has developed a technique to inject/introduce oncogenes into progenitors of connective tissue known as fibroblast cells. This induces tumor formation. By then using special stains to reveal the organelles in the resulting tumor cells, Marshall’s team can scrutinize cells at various stages of cancer growth.

“We have the trajectory of how they change as they become cancer cells. If we can move them back along the same trajectory, we’ll see if that can arrest the cancer growth.”

It’s a long way from a fundamental insight to an approved therapy, and Marshall is the first to admit it. But he says UCSF’s precision medicine mindset will likely play a key role in making that journey more quickly.

“I think the standard drug therapy approach is often a ‘fire and forget’ strategy – like a ballistic missile. You pick the drug, you give it to the patient, and cross your fingers that it will work. But precision medicine entails following up with more research to measure how the individual patient is responding – through physiological indicators or gene expression patterns or, if our organelle-based approaches pan out, measuring at the level of cellular structure.”

Precision medicine, then, extends the process into an ongoing, evidence-based approach to find not only whether a patient got better, but how and why and at what rate.

“This will allow us to steer patients back to a more healthy state instead of only hammering them with drugs,” Marshall says.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

RNA-Based Drugs Give More Control Over Gene Editing
CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes.
Monday, November 23, 2015
Some 3-D Printed Objects Are Toxic
Researchers at the University of California, Riverside have found parts produced by some commercial 3-D printers are toxic to certain fish embryos.
Monday, November 09, 2015
Artificial Kidney Research Gets A Boost
Development of a surgically implantable, artificial kidney — a promising alternative to kidney transplantation or dialysis for people with end-stage kidney disease — has received a $6 million boost.
Monday, November 09, 2015
Clearest Ever Images of Enzyme that Plays Key Roles in Aging, Cancer
UCLA-led research on telomerase could lead to new strategies for treating disease
Monday, October 19, 2015
Crop Cure
Scientists in new center to use medical research techniques to help food crops withstand drought and climate change.
Friday, October 16, 2015
Rare Childhood Leukemia Reveals Surprising Genetic Secrets
A coalition of leukemia researchers led by scientists from UC San Francisco has discovered surprising genetic diversity in juvenile myelomonocytic leukemia (JMML), a rare but aggressive childhood blood cancer.
Thursday, October 15, 2015
Sustaining Our Salad
Improving lettuce crops is the aim of a new, $4.5 million grant, awarded to University of California, Davis, researchers by the U.S. Department of Agriculture's National Institute of Food and Agriculture.
Thursday, October 15, 2015
Double Enzyme Hit May Explain Common Cancer Drug Side Effect
Mouse study suggests genomic screening before treatment may help prevent anemia.
Wednesday, October 14, 2015
New Autism Genes Are Revealed in Largest-Ever Study
Work draws more detailed picture of genetic risk, sheds light on sex differences in diagnosis.
Wednesday, September 30, 2015
Influenza A Viruses More Likely To Emerge In East Asia Than North America
Novel strains of influenza A are more likely to emerge in East Asia than in North America, according to a global analysis by the One Health Institute at the UC Davis School of Veterinary Medicine and EcoHealth Alliance.
Wednesday, September 30, 2015
Opening the Door to Safer, More Precise Cancer Therapies
New method regulates when, and how strongly, cancer-killing therapeutic T cells are activated.
Tuesday, September 29, 2015
Crunching Numbers to Combat Cancer
UCSF receives $5 million to integrate data from cancer research models.
Wednesday, September 16, 2015
Virus In Cattle Linked To Human Breast Cancer
A new study by UC Berkeley researchers establishes for the first time a link between infection with the bovine leukemia virus and human breast cancer.
Wednesday, September 16, 2015
Ultrafast DNA Diagnostics
New technology developed by UC Berkeley bioengineers promises to make a workhorse lab tool cheaper, more portable and many times faster by accelerating the heating and cooling of genetic samples with the switch of a light.
Monday, August 03, 2015
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
Kitchen Utensils Can Spread Bacteria Between Foods
In a recent study researchers found that produce that contained bacteria would contaminate other produce items through the continued use of knives or graters—the bacteria would latch on to the utensils commonly found in consumers' homes and spread to the next item.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Safer, Faster Way To Remove Pollutants From Water
Using nanoparticles filled with enzymes proves more effective than current methods.
Drug May Prevent Life-Threatening Muscle Loss in Advanced Cancers
New data describes how an experimental drug can stop life-threatening muscle wasting (cachexia) associated with advanced cancers and restore muscle health.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Novel Tumor Treatment
In the first published results from a $386,000 National Cancer Institute grant awarded earlier this year, a paper by Scott Verbridge and Rafael Davalos has been published.
Speeding Up the Process of Making Vaccines
System uses a freeze-dry concept to develop "just-add-water" solution.
Chemical Design Made Easier
Rice University scientists prepare elusive organocatalysts for drug and fine chemical synthesis.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos