UC San Diego Moores Cancer Center

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

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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.

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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.

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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.”

ucsdhealthsciences:

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.

Can you get sunburned on a cloudy day? What SPF is most effective? How often should I reapply sun lotion? May is Melanoma Awareness Month, and as summer approaches, it’s important to know the answers to these questions to avoid the dark side of the sun. In this video, Gregory Daniels, MD, PhD, talks about about skin cancer, including the warning signs, treatment options and what types of sunscreen you should be packing in your suitcase before taking off on vacation.

Molecular Tumor Board Helps in Advanced Cancer Cases

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With accelerating development of personalized cancer treatments matched to a patient’s DNA sequencing, proponents say frontline physicians increasingly need help to maneuver through the complex genomic landscape to find the most effective, individualized therapy.

In a paper published in the May 5 online issue of The Oncologist, researchers at the University of California, San Diego School of Medicine and Moores Cancer Center detail their experience evaluating 34 patients between December 2012 and June 2013 using a molecular tumor board – a new type of advisory group comprised of multidisciplinary experts, including those in the fields of tumor genetics, basic science and bioinformatics.

“Next generation sequencing tools were used to profile patients’ tumors,” said Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at UC San Diego Moores Cancer Center. In the 34 cases examined, no two patients shared the same genomic abnormalities. “We found 74 genes with 123 aberrations involved in cancer growth. Technology is permitting us to look at the molecular level of tumors, but most physicians are not trained in advanced genomics. We need access to experts in fundamental molecular biology to translate the data.”

The Moores Cancer Center’s Molecular Tumor Board brought together medical, surgical and radiation therapy oncologists, biostatisticians, radiologists, pathologists, clinical geneticists, basic and translational science researchers, and bioinformatics and pathway analysis specialists to discuss the intricacies of tumor genetics and tailor a personalized treatment plan for patients with advanced cancer or who have exhausted standard therapies.

Of the 123 abnormalities found in the patients’ genetic cancer profiles, 107 of these irregularities appeared only once. “Cancer can be different in every patient,” said Barbara Parker, MD, Moores Cancer Center deputy director for Clinical Affairs. “Standard therapy can be very efficient for many patients, but for those who do not respond to conventional treatment we need to find alternatives that will work for their disease.”

For 12 patients studied who had failed to respond to conventional therapy, treatment plans were modified according to the results of their genomic testing and the Molecular Tumor Board’s input.

“Three of the patients who had personalized cancer treatment plans discussed at the Molecular Tumor board had a partial response,” said Richard Schwab, MD, Moores Cancer Center hematology oncologist and co-director of the Biorepository and Tissue Technology Shared Resource. “Developing a plan tailored to a patient’s genetic makeup is helping us treat patients who are not responding to standard care or whose disease may have become drug resistant.”

Other patients in the study had their molecular profiling done while they were receiving treatment that was still working for them because their physicians anticipated that the therapy would become ineffective. The results of genomic matching in these patients are not yet available. Some patients could not be treated on the basis of Molecular Tumor Board discussions because there was no clinical trial for which they were eligible or because insurance would not cover the discussed medications.

“We have found that molecular diagnostics play an important role in patient care when paired with the expertise of a molecular tumor board,” said Maria Schwaederle, PharmD, lead author and a researcher in the Center for Personalized Cancer Therapy. “However, the immense complexity of tumors and their genomic aberrations will require sophisticated computer technologies for optimal interpretation, and patients need access to more clinical trials and to targeted drugs.”

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Damage Control: Recovering From Radiation and ChemotherapyProtein discovery could boost efficacy of bone marrow replacement treatments
Researchers at the University of California, San Diego School of Medicine report that a protein called beta-catenin plays a critical, and previously unappreciated, role in promoting recovery of stricken hematopoietic stem cells after radiation exposure.
The findings, published in the May 1 issue of Genes and Development, provide a new understanding of how radiation impacts cellular and molecular processes, but perhaps more importantly, they suggest new possibilities for improving hematopoietic stem cell regeneration in the bone marrow following cancer radiation treatment.
Ionizing radiation exposure – accidental or deliberate – can be fatal due to widespread destruction of hematopoietic stem cells, the cells in the bone marrow that give rise to all blood cells. A number of cancer treatments involve irradiating malignancies, essentially destroying all exposed blood cells, followed by transplantation of replacement stem cells to rebuild blood stores. The effectiveness of these treatments depends upon how well the replacement hematopoietic stem cells do their job.
In their new paper, principal investigator Tannishtha Reya, PhD, professor in the department of pharmacology, and colleagues used mouse models to show that radiation exposure triggers activation of a fundamental cellular signaling pathway called Wnt in hematopoietic stem and progenitor cells.
“The Wnt pathway and its key mediator, beta catenin, are critical for embryonic development and establishment of the body plan,” said Reya, who also works at the Sanford Consortium for Regenerative Medicine. “In addition, the Wnt pathway is activated in stem cells from many tissues and is needed for their continued maintenance.”
The researchers found that mice deficient in beta-catenin lacked the ability to activate canonical Wnt signaling and suffered from impaired hematopoietic stem cell regeneration and bone marrow recovery after radiation. Specifically, mouse hematopoietic stem cells without beta-catenin could not suppress the production of oxidative stress molecules that damage cell structures. As a result, they could not recover effectively after radiation or chemotherapy.
More here
Pictured: The continuous, necessary production of blood cells, including these red blood cells captured in a scanning micrograph by Thomas Deerinck, is the responsibility of hematopoietic stem cells found in bone marrow.

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Damage Control: Recovering From Radiation and Chemotherapy
Protein discovery could boost efficacy of bone marrow replacement treatments

Researchers at the University of California, San Diego School of Medicine report that a protein called beta-catenin plays a critical, and previously unappreciated, role in promoting recovery of stricken hematopoietic stem cells after radiation exposure.

The findings, published in the May 1 issue of Genes and Development, provide a new understanding of how radiation impacts cellular and molecular processes, but perhaps more importantly, they suggest new possibilities for improving hematopoietic stem cell regeneration in the bone marrow following cancer radiation treatment.

Ionizing radiation exposure – accidental or deliberate – can be fatal due to widespread destruction of hematopoietic stem cells, the cells in the bone marrow that give rise to all blood cells. A number of cancer treatments involve irradiating malignancies, essentially destroying all exposed blood cells, followed by transplantation of replacement stem cells to rebuild blood stores. The effectiveness of these treatments depends upon how well the replacement hematopoietic stem cells do their job.

In their new paper, principal investigator Tannishtha Reya, PhD, professor in the department of pharmacology, and colleagues used mouse models to show that radiation exposure triggers activation of a fundamental cellular signaling pathway called Wnt in hematopoietic stem and progenitor cells.

“The Wnt pathway and its key mediator, beta catenin, are critical for embryonic development and establishment of the body plan,” said Reya, who also works at the Sanford Consortium for Regenerative Medicine. “In addition, the Wnt pathway is activated in stem cells from many tissues and is needed for their continued maintenance.”

The researchers found that mice deficient in beta-catenin lacked the ability to activate canonical Wnt signaling and suffered from impaired hematopoietic stem cell regeneration and bone marrow recovery after radiation. Specifically, mouse hematopoietic stem cells without beta-catenin could not suppress the production of oxidative stress molecules that damage cell structures. As a result, they could not recover effectively after radiation or chemotherapy.

More here

Pictured: The continuous, necessary production of blood cells, including these red blood cells captured in a scanning micrograph by Thomas Deerinck, is the responsibility of hematopoietic stem cells found in bone marrow.

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