UC San Diego Moores Cancer Center

Our mission is to save lives by transforming cancer prevention, detection and care.

Prostate Cancer Diagnosis Improves with MRI Technology

An ultrasound machine provides an imperfect view of the prostate, resulting in an under-diagnosis of cancer, said J. Kellogg Parsons, MD, MHS, an UC San Diego Moores Cancer Center urologic oncologist. Patients who have rising prostate-specific antigen (PSA) levels, a protein that is often elevated in men with prostate cancer, but who have not been diagnosed with cancer could benefit from the new use of MRI images in combination with the traditional prostate biopsy. The technology offers physicians a new view and changes the patient experience by reducing the number of false-positive biopsies and resulting in earlier diagnosis when cancer is present, said Dr. Parsons. 

In this video, Dr. Parsons explains how the procedure works while one of his patients describes his experience with prostate cancer and diagnosis.

As science continues to reveal more about cancer, you may notice that research seems to contradict what we previously knew to be true about this disease. Read about the newest cancer research but discuss with your medical team what applies to you. Remember, no two cancers are the same. 
David A. Cheresh, PhD, Associate Director for Innovation and Industry Alliances at UC San Diego Moores Cancer Center, and colleagues have found a link between breast cancer and pregnancy. However, they caution that the findings should not be interpreted as a reason to avoid pregnancy as the cancer does not appear to be caused by the pregnancy itself. Read the full story from our sister blog.  

ucsdhealthsciences:

How Breast Cancer Usurps the Powers of Mammary Stem Cells
During pregnancy, certain hormones trigger specialized mammary stem cells to create milk-producing cells essential to lactation. Scientists at the University of California, San Diego School of Medicine and Moores Cancer Center have found that mammary stem cells associated with the pregnant mammary gland are related to stem cells found in breast cancer. 
Writing in the August 11, 2014 issue of Developmental Cell, David A. Cheresh, PhD, Distinguished Professor of Pathology and vice-chair for research and development, Jay Desgrosellier, PhD, assistant professor of pathology and colleagues specifically identified a key molecular pathway associated with aggressive breast cancers that is also required for mammary stem cells to promote lactation development during pregnancy. 
“By understanding a fundamental mechanism of mammary gland development during pregnancy, we have gained a rare insight into how aggressive breast cancer might be treated,” said Cheresh. “This pathway can be exploited. Certain drugs are known to disrupt this pathway and may interfere with the process of breast cancer progression.”
During pregnancy, a new mammary stem cell population arises, distinct from those involved in development and maintenance of the non-pregnant gland. These stem cells remodel the breasts and lactating glands in preparation for feeding the newborn child. Normally, these stem cells contribute only to early remodeling events and are switched off by the time milk production begins.
The researchers found, however, that signals regulating stem cell activation during pregnancy appear to be hijacked by cancer cells to produce faster-growing, more aggressive tumors. “This normal pathway ends up contributing to the progression of cancer,” said Desgrosellier, first author of the study.
A connection between pregnancy and breast cancer has long been known. But the association between pregnancy and breast cancer risk is complex. While having a child reduces a woman’s risk of developing breast cancer later in life, there is also an increased short-term risk for the development of a highly aggressive form of breast cancer following each pregnancy. The current study suggests that molecules important for stem cell behavior during pregnancy may contribute to these more aggressive pregnancy-associated breast cancers, a possibility the researchers plan to investigate further.
The authors are quick to point out that their findings should not be interpreted as a reason to avoid pregnancy. The signaling pathway usurped by cancer cells is not the cause of breast cancer. Rather, they said, it may worsen or accelerate a cancer caused by other factors, such as an underlying mutation or genetic predisposition.
“Our work doesn’t speak to the actual cause of cancer. Rather, it explains what can happen once cancer has been initiated,” said Cheresh. “Here’s an analogy: To get cancer, you first have to start with an oncogene, a gene that carries a mutation and has the potential to initiate cancer. Think of the oncogene as turning on a car’s ignition. The signaling pathway exploited by cancer cells is like applying gas. It gets the car moving, but it means nothing if the oncogene hasn’t first started the process.”
The researchers focused on a family of cell surface receptor proteins called integrins that act as key communications conduits, ultimately zeroing in on the role of one member of this family called beta-3 integrin. Also known as CD61, it was already linked to metastasis and resistance to cancer drugs.
Cheresh noted that CD61 represents a good marker for the incriminated signaling pathway involved in both mammary development during pregnancy and cancer. It’s easily detected and could be used to both diagnose and treat breast cancer cases. “Detecting CD61 might help doctors determine what kind of therapeutic approach to use, knowing that they might be dealing with a more aggressive yet treatable form of breast cancer. For example, there are existing drugs that block CD61 signaling, which might be another potential aspect of treatment.”

As science continues to reveal more about cancer, you may notice that research seems to contradict what we previously knew to be true about this disease. Read about the newest cancer research but discuss with your medical team what applies to you. Remember, no two cancers are the same. 

David A. Cheresh, PhDAssociate Director for Innovation and Industry Alliances at UC San Diego Moores Cancer Center, and colleagues have found a link between breast cancer and pregnancy. However, they caution that the findings should not be interpreted as a reason to avoid pregnancy as the cancer does not appear to be caused by the pregnancy itself. Read the full story from our sister blog.  

ucsdhealthsciences:

How Breast Cancer Usurps the Powers of Mammary Stem Cells

During pregnancy, certain hormones trigger specialized mammary stem cells to create milk-producing cells essential to lactation. Scientists at the University of California, San Diego School of Medicine and Moores Cancer Center have found that mammary stem cells associated with the pregnant mammary gland are related to stem cells found in breast cancer. 

Writing in the August 11, 2014 issue of Developmental Cell, David A. Cheresh, PhD, Distinguished Professor of Pathology and vice-chair for research and development, Jay Desgrosellier, PhD, assistant professor of pathology and colleagues specifically identified a key molecular pathway associated with aggressive breast cancers that is also required for mammary stem cells to promote lactation development during pregnancy. 

“By understanding a fundamental mechanism of mammary gland development during pregnancy, we have gained a rare insight into how aggressive breast cancer might be treated,” said Cheresh. “This pathway can be exploited. Certain drugs are known to disrupt this pathway and may interfere with the process of breast cancer progression.”

During pregnancy, a new mammary stem cell population arises, distinct from those involved in development and maintenance of the non-pregnant gland. These stem cells remodel the breasts and lactating glands in preparation for feeding the newborn child. Normally, these stem cells contribute only to early remodeling events and are switched off by the time milk production begins.

The researchers found, however, that signals regulating stem cell activation during pregnancy appear to be hijacked by cancer cells to produce faster-growing, more aggressive tumors. “This normal pathway ends up contributing to the progression of cancer,” said Desgrosellier, first author of the study.

A connection between pregnancy and breast cancer has long been known. But the association between pregnancy and breast cancer risk is complex. While having a child reduces a woman’s risk of developing breast cancer later in life, there is also an increased short-term risk for the development of a highly aggressive form of breast cancer following each pregnancy. The current study suggests that molecules important for stem cell behavior during pregnancy may contribute to these more aggressive pregnancy-associated breast cancers, a possibility the researchers plan to investigate further.

The authors are quick to point out that their findings should not be interpreted as a reason to avoid pregnancy. The signaling pathway usurped by cancer cells is not the cause of breast cancer. Rather, they said, it may worsen or accelerate a cancer caused by other factors, such as an underlying mutation or genetic predisposition.

“Our work doesn’t speak to the actual cause of cancer. Rather, it explains what can happen once cancer has been initiated,” said Cheresh. “Here’s an analogy: To get cancer, you first have to start with an oncogene, a gene that carries a mutation and has the potential to initiate cancer. Think of the oncogene as turning on a car’s ignition. The signaling pathway exploited by cancer cells is like applying gas. It gets the car moving, but it means nothing if the oncogene hasn’t first started the process.”

The researchers focused on a family of cell surface receptor proteins called integrins that act as key communications conduits, ultimately zeroing in on the role of one member of this family called beta-3 integrin. Also known as CD61, it was already linked to metastasis and resistance to cancer drugs.

Cheresh noted that CD61 represents a good marker for the incriminated signaling pathway involved in both mammary development during pregnancy and cancer. It’s easily detected and could be used to both diagnose and treat breast cancer cases. “Detecting CD61 might help doctors determine what kind of therapeutic approach to use, knowing that they might be dealing with a more aggressive yet treatable form of breast cancer. For example, there are existing drugs that block CD61 signaling, which might be another potential aspect of treatment.”

Photo credit: “Chili (633442211)” by Randi Hausken from Bærum, Norway - Chili Uploaded by russavia. Licensed under Creative Commons Attribution-Share Alike 2.0 via Wikimedia Commons 



Food for thought: Chili peppers are more than spice in your diet
Attend one of our free Healing Foods Kitchen cooking classes and you’ll hear Susan Faerber tell you that capsaicin, the active ingredient that makes chili peppers hot, has protective benefits against cancer. In a study published in the Aug. 1 issue of The Journal of Clinical Investigation, UC San Diego Moores Cancer Center researchers say capsaicin triggers a reaction that reduces the risk of colorectal tumors.
But before you add a Carolina Reaper, the world’s hottest pepper, to one of Susan’s cancer fighting recipes or your own healthy meal, read about the science behind the study at our sister blog ucsdhealthsciences.
We asked the researchers to break down this spicy news for our own consumption and tell us what does it mean for you and me? Do countries with a traditionally high use of chili peppers in their diet see lower incidence of colorectal cancer?
The answer is a bit complicated and we must be cautious to infer any cause-and-effect relationships from epidemiological data, said Petrus de Jong, MD, first author of the study. Still, a 2009 study on colorectal cancer incidence shows there are benefits.
“Countries with a high dietary intake of capsaicinoids (e.g. India, Bangladesh, Thailand, Mexico) show a five to 10-fold lower incidence of colorectal cancer compared to Western countries,” said Dr. de Jong.
“Various factors may be associated with the reduced incidence of colorectal cancer in these countries, including dietary factors such as low consumption of red meats and high consumption of non-starch polysaccharides, vegetables and phytochemicals (i.e. capsaicin). Indeed, a shift from a traditional Mexican to a predominantly Western diet has been associated with an increased risk of this cancer as shown by a 2003 study.”
So there is a benefit! But, how much do we need to eat?
“A significant anti-tumor effect would require more than just ‘a spicy diet’,” said Dr. de Jong.
The amount of capsaicin used in the experiments is at least five times higher than what the average people in countries who eat lots chili pepper consume. Dr. de Jong says a good starting point to determine how much capsaicin we need to ingest would be a feasibility study that would target the active substance mainly to the large intestine. So until then, eat your habanero, jalapeño, piri piri or the pepper of choice depending on your heat level tolerance and know that it has some health benefits in addition to adding flavor to your meals.
Bon appétit. 

Photo credit: “Chili (633442211)” by Randi Hausken from Bærum, Norway - Chili Uploaded by russavia. Licensed under Creative Commons Attribution-Share Alike 2.0 via Wikimedia Commons

Food for thought: Chili peppers are more than spice in your diet

Attend one of our free Healing Foods Kitchen cooking classes and you’ll hear Susan Faerber tell you that capsaicin, the active ingredient that makes chili peppers hot, has protective benefits against cancer. In a study published in the Aug. 1 issue of The Journal of Clinical Investigation, UC San Diego Moores Cancer Center researchers say capsaicin triggers a reaction that reduces the risk of colorectal tumors.

But before you add a Carolina Reaper, the world’s hottest pepper, to one of Susan’s cancer fighting recipes or your own healthy meal, read about the science behind the study at our sister blog ucsdhealthsciences.

We asked the researchers to break down this spicy news for our own consumption and tell us what does it mean for you and me? Do countries with a traditionally high use of chili peppers in their diet see lower incidence of colorectal cancer?

The answer is a bit complicated and we must be cautious to infer any cause-and-effect relationships from epidemiological data, said Petrus de Jong, MD, first author of the study. Still, a 2009 study on colorectal cancer incidence shows there are benefits.

“Countries with a high dietary intake of capsaicinoids (e.g. India, Bangladesh, Thailand, Mexico) show a five to 10-fold lower incidence of colorectal cancer compared to Western countries,” said Dr. de Jong.

“Various factors may be associated with the reduced incidence of colorectal cancer in these countries, including dietary factors such as low consumption of red meats and high consumption of non-starch polysaccharides, vegetables and phytochemicals (i.e. capsaicin). Indeed, a shift from a traditional Mexican to a predominantly Western diet has been associated with an increased risk of this cancer as shown by a 2003 study.”

So there is a benefit! But, how much do we need to eat?

“A significant anti-tumor effect would require more than just ‘a spicy diet’,” said Dr. de Jong.

The amount of capsaicin used in the experiments is at least five times higher than what the average people in countries who eat lots chili pepper consume. Dr. de Jong says a good starting point to determine how much capsaicin we need to ingest would be a feasibility study that would target the active substance mainly to the large intestine. So until then, eat your habanero, jalapeño, piri piri or the pepper of choice depending on your heat level tolerance and know that it has some health benefits in addition to adding flavor to your meals.

Bon appétit. 

From our sister blog, a new look at appendix cancer that may lead to new and improved therapies for this rare disease.

ucsdhealthsciences:

Study gives promise to new treatment for appendix cancer
Appendix cancer is rare, with approximately 600 to 1,000 new patients diagnosed each year and an estimated 10,000 currently living with the disease. Because it is rare, few studies have been devoted to this cancer and standard treatment for appendix cancers relies upon the same chemotherapy drugs used for colorectal cancer. A new study by researchers at the University of California, San Diego School of Medicine has found that genetic mutations in appendix and colon cancers are, in fact, quite different, suggesting that new and different approaches to appendix cancer treatment should be explored.
The study was published in a recent issue of Genome Medicine.
Cancers are characterized by different gene mutations. Historically, genetic mutations in appendix cancer have been poorly characterized due to its low incidence. The cancer often remains undiagnosed until it is discovered during or after abdominal surgery or when an abnormal mass is detected  during a CT scan for an unrelated condition.
The primary treatment of localized appendix cancer is surgical but treatment for patients with inoperable appendix cancer has been limited to therapies developed for colorectal cancer. Although the chemotherapy drugs used for colorectal cancer dramatically improve patient outcomes, they have not proven to be as successful in patients with appendix cancer.
“We have been treating appendix cancer like colorectal cancer because it was thought to be the most similar tumor type, but this study identifies the signature differences between these two cancers,” said Andrew Lowy, MD, FACS, a senior author of the study and professor of Surgery at UC San Diego School of Medicine. “These findings suggest opportunities to develop novel therapies that specifically target appendix cancer.”  
The study initially evaluated 10 cases, nine with low-grade appendix cancers and one with high-grade cancer. The results from this group were then validated with 19 additional cases.
The results also identified a gene mutation in appendix cancer that is commonly found in a form of pancreatic cancer, which typically spreads rapidly and is seldom detected in its early stages.
“The study’s results are promising for patients. We now have a more in-depth knowledge of the biological make up of appendix cancers, which allow for a more customized approach,” said Lowy, who also serves as chief of the Division of Surgical Oncology at UC San Diego Health System. “The goal is to now conduct more studies that will test specific treatments targeted to these unique genetic mutations.”
To learn more about cancer treatments at UC San Diego Health System, visit cancer.ucsd.edu         Image: A histopathological photomicrograph depicting cancerous cells in the appendix.

From our sister blog, a new look at appendix cancer that may lead to new and improved therapies for this rare disease.

ucsdhealthsciences:

Study gives promise to new treatment for appendix cancer

Appendix cancer is rare, with approximately 600 to 1,000 new patients diagnosed each year and an estimated 10,000 currently living with the disease. Because it is rare, few studies have been devoted to this cancer and standard treatment for appendix cancers relies upon the same chemotherapy drugs used for colorectal cancer. A new study by researchers at the University of California, San Diego School of Medicine has found that genetic mutations in appendix and colon cancers are, in fact, quite different, suggesting that new and different approaches to appendix cancer treatment should be explored.

The study was published in a recent issue of Genome Medicine.

Cancers are characterized by different gene mutations. Historically, genetic mutations in appendix cancer have been poorly characterized due to its low incidence. The cancer often remains undiagnosed until it is discovered during or after abdominal surgery or when an abnormal mass is detected  during a CT scan for an unrelated condition.

The primary treatment of localized appendix cancer is surgical but treatment for patients with inoperable appendix cancer has been limited to therapies developed for colorectal cancer. Although the chemotherapy drugs used for colorectal cancer dramatically improve patient outcomes, they have not proven to be as successful in patients with appendix cancer.

“We have been treating appendix cancer like colorectal cancer because it was thought to be the most similar tumor type, but this study identifies the signature differences between these two cancers,” said Andrew Lowy, MD, FACS, a senior author of the study and professor of Surgery at UC San Diego School of Medicine. “These findings suggest opportunities to develop novel therapies that specifically target appendix cancer.”  

The study initially evaluated 10 cases, nine with low-grade appendix cancers and one with high-grade cancer. The results from this group were then validated with 19 additional cases.

The results also identified a gene mutation in appendix cancer that is commonly found in a form of pancreatic cancer, which typically spreads rapidly and is seldom detected in its early stages.

“The study’s results are promising for patients. We now have a more in-depth knowledge of the biological make up of appendix cancers, which allow for a more customized approach,” said Lowy, who also serves as chief of the Division of Surgical Oncology at UC San Diego Health System. “The goal is to now conduct more studies that will test specific treatments targeted to these unique genetic mutations.”

To learn more about cancer treatments at UC San Diego Health System, visit cancer.ucsd.edu        

Image: A histopathological photomicrograph depicting cancerous cells in the appendix.

ucsdhealthsciences:

Finding the Achilles’ Heel of Ovarian Tumor Growth
A team of scientists, led by principal investigator David D. Schlaepfer, PhD, professor in the Department of Reproductive Medicine at the University of California, San Diego School of Medicine report that small molecule inhibitors to a protein called focal adhesion kinase (FAK) selectively prevent the growth of ovarian cancer cells as tumor spheroids.
The findings come in a pair of studies published online this week in the journals Gynecologic Oncology and Molecular Cancer Therapeutics.
Ovarian cancer is a leading cause of female cancer death in the United States. On average, more than 21,000 women are diagnosed with ovarian cancer each year and 14,270 die. Many women achieve remission, but cancer recurrence rates exceed 75 percent, prompting the need for new treatments.
“Ovarian cancer spreads within a women’s peritoneal space through a unique mechanism that involves the survival of small clusters of tumor cells termed spheroids,” said Schlaepfer. “Our studies show that FAK signaling functions at the center of a tumor cell survival signaling network.”
In the first study, published in Gynecologic Oncology, first author Nina Shah, MD, a gynecological oncology fellow in the Department of Reproductive Medicine, found that ovarian tumor cells with low levels of a tumor suppressor protein, called merlin, displayed heightened sensitivity to FAK inhibitor growth cessation.
“With FAK inhibitor clinical trials already testing a similar linkage in mesothelioma (a rare cancer that affects the protective lining of many internal organs), our results support the hypothesis that protein biomarkers such as merlin may identify those patients who may best respond to FAK inhibitor therapy,” said Schlaepfer.
In the second study in Molecular Cancer Therapeutics, first author Isabelle Tancioni PhD, an assistant project scientist at UC San Diego Moores Cancer Center discovered that a network of signals generated by osteopontin – a beta-5 integrin receptor used in cell-to-cell signaling – and FAK control ovarian cancer spheroid growth. High levels of beta-5 integrin and FAK expression are associated with a poor prognosis for some ovarian cancer patients. “Thus, high levels of beta-5 integrin may serve as a novel biomarker for ovarian carcinoma cells that possess active FAK signaling,” said Schlaepfer.
Schlaepfer noted that tumor recurrence and metastasis are responsible for the majority of ovarian cancer-related deaths and said the new findings support ongoing clinical trials of FAK inhibitors as new agents in the fight to prevent ovarian cancer progression.

ucsdhealthsciences:

Finding the Achilles’ Heel of Ovarian Tumor Growth

A team of scientists, led by principal investigator David D. Schlaepfer, PhD, professor in the Department of Reproductive Medicine at the University of California, San Diego School of Medicine report that small molecule inhibitors to a protein called focal adhesion kinase (FAK) selectively prevent the growth of ovarian cancer cells as tumor spheroids.

The findings come in a pair of studies published online this week in the journals Gynecologic Oncology and Molecular Cancer Therapeutics.

Ovarian cancer is a leading cause of female cancer death in the United States. On average, more than 21,000 women are diagnosed with ovarian cancer each year and 14,270 die. Many women achieve remission, but cancer recurrence rates exceed 75 percent, prompting the need for new treatments.

“Ovarian cancer spreads within a women’s peritoneal space through a unique mechanism that involves the survival of small clusters of tumor cells termed spheroids,” said Schlaepfer. “Our studies show that FAK signaling functions at the center of a tumor cell survival signaling network.”

In the first study, published in Gynecologic Oncology, first author Nina Shah, MD, a gynecological oncology fellow in the Department of Reproductive Medicine, found that ovarian tumor cells with low levels of a tumor suppressor protein, called merlin, displayed heightened sensitivity to FAK inhibitor growth cessation.

“With FAK inhibitor clinical trials already testing a similar linkage in mesothelioma (a rare cancer that affects the protective lining of many internal organs), our results support the hypothesis that protein biomarkers such as merlin may identify those patients who may best respond to FAK inhibitor therapy,” said Schlaepfer.

In the second study in Molecular Cancer Therapeutics, first author Isabelle Tancioni PhD, an assistant project scientist at UC San Diego Moores Cancer Center discovered that a network of signals generated by osteopontin – a beta-5 integrin receptor used in cell-to-cell signaling – and FAK control ovarian cancer spheroid growth. High levels of beta-5 integrin and FAK expression are associated with a poor prognosis for some ovarian cancer patients. “Thus, high levels of beta-5 integrin may serve as a novel biomarker for ovarian carcinoma cells that possess active FAK signaling,” said Schlaepfer.

Schlaepfer noted that tumor recurrence and metastasis are responsible for the majority of ovarian cancer-related deaths and said the new findings support ongoing clinical trials of FAK inhibitors as new agents in the fight to prevent ovarian cancer progression.

Six new guidelines published in the Journal of the American College of Nutrition describe ways to reduce a person’s risk of cancer. Gordon Saxe, MD, PhD, a ucsdhealthsciences researcher and physician, says cancer rates are substantially higher in the United States due in part to diet. The guidelines he helped draft advise people to avoid or limit exposure to red meat, grilled meats, alcohol and dairy while increasing consumption of fresh fruits and vegetables.

Look for nutrition classes that offer ways to blend more fruits and vegetables into your diet in way that even picky eaters will enjoy. At UC San Diego Moores Cancer Center we offer free, monthly cooking classes that include recipes, food demonstrations and tasting at the Healing Foods Kitchen.

ucsdhealthsciences:

Melanoma of the Eye Caused by Two Gene Mutations
Researchers at the University of California, San Diego School of Medicine have identified a therapeutic target for treating the most common form of eye cancer in adults. They have also, in experiments with mice, been able to slow eye tumor growth with an existing FDA-approved drug.
The findings are published online in the May 29 issue of the journal Cancer Cell.
“The beauty of our study is its simplicity,” said Kun-Liang Guan, PhD, professor of pharmacology at UC San Diego Moores Cancer Center and co-author of the study. “The genetics of this cancer are very simple and our results have clear implications for therapeutic treatments for the disease.”
The researchers looked specifically at uveal melanoma. Uveal collectively refers to parts of the eye, notably the iris, that contain pigment cells. As with melanoma skin cancer, uveal melanoma is a malignancy of these melanin-producing cells.
Approximately 2,000 people in the United States are diagnosed with uveal melanoma each year. If the cancer is restricted to just the eye, the standard treatment is radiation and surgical removal of the eye. But uveal melanoma often spreads to the liver, and determining the metastatic status of the disease can be difficult. In cases of uveal melanoma metastasis, patients typically succumb within two to eight months after diagnosis.
Scientists have long suspected a genetic association with uveal melanoma because one of two gene mutations is present in approximately 70 percent of all tumors. Until this study, however, they had not identified a mechanism that could explain why and how these mutations actually caused tumors.
The work by Guan and colleagues unravels the causal relationship between the genetic mutations and tumor formation, and identifies a molecular pathway along which drugs might counterattack.
The two genes implicated – GNAQ and GNA11 – code for proteins (known as G proteins) that normally function as molecular on-off switches, regulating the passage of information from the outside to the inside of a cell.
In their experiments, the scientists showed that mutations in these genes shift the G proteins to a permanent “on” or active status, which results in over-activation the Yes-associated protein (YAP). The activation of the YAP protein induces uncontrolled cell growth and inhibits cell death, causing malignancies.
Earlier research by other scientists has shown that the drug verteporfin, used to treat abnormal blood vessel formation in the eye, acts on the YAP pathway inhibiting the protein’s YAP function.
In experiments with mice, the UC San Diego-led team showed that verteporfin also suppresses the growth of uveal melanoma tumors derived from human tumors.
“We have a cancer that is caused by a very simple genetic mechanism,” Guan said. “And we have a drug that works on this mechanism. The clinical applications are very direct.”
Pictured: An untreated uveal melanoma tumor (left) covers entire eye of a mouse. A tumor treated with verteporfin (right) is smaller and much of the structure of the mouse’s eye is visible.

ucsdhealthsciences:

Melanoma of the Eye Caused by Two Gene Mutations

Researchers at the University of California, San Diego School of Medicine have identified a therapeutic target for treating the most common form of eye cancer in adults. They have also, in experiments with mice, been able to slow eye tumor growth with an existing FDA-approved drug.

The findings are published online in the May 29 issue of the journal Cancer Cell.

“The beauty of our study is its simplicity,” said Kun-Liang Guan, PhD, professor of pharmacology at UC San Diego Moores Cancer Center and co-author of the study. “The genetics of this cancer are very simple and our results have clear implications for therapeutic treatments for the disease.”

The researchers looked specifically at uveal melanoma. Uveal collectively refers to parts of the eye, notably the iris, that contain pigment cells. As with melanoma skin cancer, uveal melanoma is a malignancy of these melanin-producing cells.

Approximately 2,000 people in the United States are diagnosed with uveal melanoma each year. If the cancer is restricted to just the eye, the standard treatment is radiation and surgical removal of the eye. But uveal melanoma often spreads to the liver, and determining the metastatic status of the disease can be difficult. In cases of uveal melanoma metastasis, patients typically succumb within two to eight months after diagnosis.

Scientists have long suspected a genetic association with uveal melanoma because one of two gene mutations is present in approximately 70 percent of all tumors. Until this study, however, they had not identified a mechanism that could explain why and how these mutations actually caused tumors.

The work by Guan and colleagues unravels the causal relationship between the genetic mutations and tumor formation, and identifies a molecular pathway along which drugs might counterattack.

The two genes implicated – GNAQ and GNA11 – code for proteins (known as G proteins) that normally function as molecular on-off switches, regulating the passage of information from the outside to the inside of a cell.

In their experiments, the scientists showed that mutations in these genes shift the G proteins to a permanent “on” or active status, which results in over-activation the Yes-associated protein (YAP). The activation of the YAP protein induces uncontrolled cell growth and inhibits cell death, causing malignancies.

Earlier research by other scientists has shown that the drug verteporfin, used to treat abnormal blood vessel formation in the eye, acts on the YAP pathway inhibiting the protein’s YAP function.

In experiments with mice, the UC San Diego-led team showed that verteporfin also suppresses the growth of uveal melanoma tumors derived from human tumors.

“We have a cancer that is caused by a very simple genetic mechanism,” Guan said. “And we have a drug that works on this mechanism. The clinical applications are very direct.”

Pictured: An untreated uveal melanoma tumor (left) covers entire eye of a mouse. A tumor treated with verteporfin (right) is smaller and much of the structure of the mouse’s eye is visible.

ucsdhealthsciences:

Cancer Avatars for Personalized MedicineTumor modeling predicts most effective drugs targeting brain cancer
Researchers at University of California, San Diego School of Medicine and Moores Cancer Center have used computer simulations of cancer cells – cancer avatars – to identify drugs most likely to kill cancer cells isolated from patients’ brain tumors.
The findings, published in May 21 online issue of the Journal of Translational Medicine, may help researchers stratify cancer patients for clinical trials according to their cancers’ genomic signatures and predicted sensitivities to different cancer drugs.
Such an approach would allow scientists to selectively test cancer drugs on those who would be most likely to respond to them, while simultaneously reducing patients’ exposures to toxic drugs that would likely be ineffective.
“Genomics tells us that cancers are a lot like snowflakes. No two cancers are alike so it does not make sense to give all patients the same drugs. This is the idea behind personalizing therapies for cancer,” said lead author Sandeep Pingle, MD, PhD, a project scientist in the laboratory of Santosh Kesari, MD, PhD, chief of the division of Neuro-Oncology, professor in the department of neurosciences, director of Neuro-Oncology at UC San Diego Moores Cancer Center and the study’s senior author.
“With the virtual cell model, we can take into account all the complexity of cellular processes to predict which drugs will be the most effective against a particular tumor based on its genomic profile,” Pingle said. “This is a first step toward personalized medicine.”
Researchers developed a virtual cell that represents the internal workings of a normal, healthy cell, depicting them as a complex collection of signaling pathways and metabolic networks. The virtual healthy cell can be made cancerous. Indeed, it can be turned into any kind of cancer cell by distorting specific points and pathways in the system. These cellular distortions represent a person’s so-called cancer avatar. Once the avatar is generated, a computer model predicts which drugs, based upon their known functions, are most likely to kill a real cancer cell.
For the study, researchers generated cancer avatars for cells obtained from patients with glioblastoma, a highly aggressive cancer of the brain’s glial cells. The condition has a five-year survival rate of about 10 percent. The computer generated predictions were then “truth-checked” against standard, cultured cells in drug-sensitivity experiments.
“The advantage of computational modeling is the ability to incorporate the wealth of genomic and proteomic information on cancer cells and to screen drugs and combinations of drugs much faster and cost effectively,” said Kesari. “Our ultimate goal is to take this technology to the clinic to identify the best drugs for treating each individual cancer patient.”

ucsdhealthsciences:

Cancer Avatars for Personalized Medicine
Tumor modeling predicts most effective drugs targeting brain cancer

Researchers at University of California, San Diego School of Medicine and Moores Cancer Center have used computer simulations of cancer cells – cancer avatars – to identify drugs most likely to kill cancer cells isolated from patients’ brain tumors.

The findings, published in May 21 online issue of the Journal of Translational Medicine, may help researchers stratify cancer patients for clinical trials according to their cancers’ genomic signatures and predicted sensitivities to different cancer drugs.

Such an approach would allow scientists to selectively test cancer drugs on those who would be most likely to respond to them, while simultaneously reducing patients’ exposures to toxic drugs that would likely be ineffective.

“Genomics tells us that cancers are a lot like snowflakes. No two cancers are alike so it does not make sense to give all patients the same drugs. This is the idea behind personalizing therapies for cancer,” said lead author Sandeep Pingle, MD, PhD, a project scientist in the laboratory of Santosh Kesari, MD, PhD, chief of the division of Neuro-Oncology, professor in the department of neurosciences, director of Neuro-Oncology at UC San Diego Moores Cancer Center and the study’s senior author.

“With the virtual cell model, we can take into account all the complexity of cellular processes to predict which drugs will be the most effective against a particular tumor based on its genomic profile,” Pingle said. “This is a first step toward personalized medicine.”

Researchers developed a virtual cell that represents the internal workings of a normal, healthy cell, depicting them as a complex collection of signaling pathways and metabolic networks. The virtual healthy cell can be made cancerous. Indeed, it can be turned into any kind of cancer cell by distorting specific points and pathways in the system. These cellular distortions represent a person’s so-called cancer avatar. Once the avatar is generated, a computer model predicts which drugs, based upon their known functions, are most likely to kill a real cancer cell.

For the study, researchers generated cancer avatars for cells obtained from patients with glioblastoma, a highly aggressive cancer of the brain’s glial cells. The condition has a five-year survival rate of about 10 percent. The computer generated predictions were then “truth-checked” against standard, cultured cells in drug-sensitivity experiments.

“The advantage of computational modeling is the ability to incorporate the wealth of genomic and proteomic information on cancer cells and to screen drugs and combinations of drugs much faster and cost effectively,” said Kesari. “Our ultimate goal is to take this technology to the clinic to identify the best drugs for treating each individual cancer patient.”

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MRI-Guided Biopsy for Brain Cancer Improves Diagnosis, California First

Neurosurgeons at UC San Diego Heath System have, for the first time, combined real-time magnetic resonance imaging (MRI) technology with novel non-invasive cellular mapping techniques to develop a new biopsy approach that increases the accuracy of diagnosis for patients with brain cancer.

“There are many different types of brain cancer. Making an accurate diagnosis is paramount because the diagnosis dictates the subsequent course of treatment,” said Clark C. Chen, MD, PhD, vice-chairman of research, division of neurosurgery, UC San Diego School of Medicine. “For instance, the treatment of glioblastoma is fundamentally different than the treatment for oligodendroglioma, another type of brain tumor.”

Chen said that as many as one third of brain tumor biopsies performed in the traditional manner can result in misdiagnosis. He cited two challenges with conventional biopsy.

“First, because distinct areas of brain tumors exhibit different cell densities and higher cell densities are generally associated with higher tumor grade, biopsies taken from one region may yield a different diagnosis than if another area is biopsied,” said Chen. “Second, because tumors are hidden within the brain, surgeons must use mathematical algorithms to target where the biopsy should occur. As with all calculations, the process is subject to errors that the surgeon cannot easily correct in real time once the biopsy has begun.”

Chen’s team applied an MRI technique called Restriction Spectrum Imaging (RSI) to visualize the parts of the brain tumor that contain different cell densities.

“RSI allows us to identify the regions of the cell that are most representative of the entire tumor,” said Chen. “By targeting biopsies to these areas, we minimize the number of biopsies needed but still achieve a sampling that best characterizes the entire tumor.”

To ensure a targeted biopsy, Chen performs the procedure in the MRI suite while the patient is under general anesthesia. Because conventional biopsy equipment cannot be used in the MRI, Chen uses a special MRI-compatible system called ClearPoint®. This system utilizes an integrated set of hardware, software, and surgical equipment to allow the surgeon to target and visualize the path of the biopsy as well as the actual biopsy site, intraoperatively.

“Surgeons have been performing brain biopsies in a near blind manner for the past fifty years. The ability to see where the biopsy needle is located and where the biopsy is being performed in real time is groundbreaking,” said Chen. “This combination of technologies gives me an opportunity to immediately adjust my surgical approach while minimizing risk.”

The study and application of RSI is currently being performed at the newly established Center for Translational Imaging and Personalized Medicine and Center for Theoretical and Applied Neuro-Oncology at UC San Diego, School of Medicine. The RSI technology was developed by Anders M. Dale, PhD, vice-chairman, Department of Radiology, UC San Diego, School of Medicine. The ClearPoint System was developed by MRI Interventions, Inc., of Irvine, CA.

To learn more about UC San Diego Health System and the multidisciplinary team at UC San Diego Moores Cancer Center, visit cancer.ucsd.edu/brain

Diagnosed with Breast Cancer? Yoga May Help

Ask people why they practice yoga and they may say they do it for its healing effects, such as improved flexibility, better sleep or reduced stress. Add another possible reason: To combat the harsh impact of breast cancer on the body.

Two research papers published earlier this year point to the improved well-being of woman who practice yoga during and after breast cancer treatment. Yoga is not simply a stretching exercise; it also incorporates controlled breathing, mediation and relaxation techniques. Do these components confer a positive effect on people being treated for breast cancer?

“Yoga has multiple components and different types of yoga have varying levels of those components,” said Erik Groessl, PhD, associate professor in the UC San Diego School of Medicine Department of Family and Preventive Medicine and Health Services Research Center director. “Yoga interventions can be tailored to specific groups like breast cancer patients, where the goals may focus more on reducing fatigue, promoting healing, improving mood and reducing stress and inflammation.”

According to a study published in the Journal of Clinical Oncology by the University of Texas MD Anderson Cancer Center, yoga’s mind and body exercises seem to hold the key to lowering stress hormones and improving the ability of women with breast cancer to engage in daily activities while they undergo radiation therapy.

Women in the study attended one-hour yoga sessions three times a week during their six week radiation treatments. Compared to control groups of women who only did stretching exercises or who had no instruction in either yoga or stretching, the women who practiced yoga had the steepest decline in stress hormones, which have been found to impact breast cancer outcomes.

In the second study published in the same journal by researchers at Ohio State University, women who participated twice a week in 90-minute yoga sessions after their last surgical or radiation treatment experienced reduced fatigue (57 percent less) than women who did not practice yoga. Inflammation was reduced by up to 20 percent in yogis.

Researchers reported that cardiorespiratory health is negatively impacted during cancer treatment. By reducing inflammation, fatigue and depression and improving sleep quality, the women were able to engage in other activities over time which improved their overall health, the study authors concluded.

Before engaging in any physical activity, talk with your physician to discuss what is right for you. And, ask your medical provider if your cancer center offers yoga for patients with cancer. UC San Diego Moores Cancer Center offers Gentle Yoga every Monday.

Namaste.

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