Plasma cfDNA Can Monitor Response To Metastatic Colon Cancer Treatment

Van K. Morris, M.D. Assistant Professor, GI Medical Oncology University of Texas – M.D. Anderson Cancer Center Houston, TX 77030

Dr. Morris

MedicalResearch.com Interview with:
Van K. Morris,  M.D.
Assistant Professor, GI Medical Oncology
University of Texas – M.D. Anderson Cancer Center
Houston, TX 77030 

Medical Research: What is the background for this study? What are the main findings?

Dr. Van K Morris: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer.  Patients were enrolled in a phase I clinical trial with the BRAF inhibitor vemurafenib, the anti-EGFR antibody cetuximab, and irinotecan.  Blood  samples were collected every two weeks with each dose, and plasma was analyzed for changes in the fraction of mutant BRAF V600E allele relative to wild-type BRAF allele with time.  Trends in circulating free DNA (cfDNA) changes were compared with radiographic changes by RECIST 1.1 criteria to examine this technique as a marker for response to therapy.

For patients who had a response radiographically, drastic reductions in the BRAF V600E allele fraction were observed even after two weeks of starting therapy, well before the first restaging scan.  Patients who did not have responses radiographically had less  dramatic changes relative to baseline in the BRAF V600E allele fraction.  This technique analyzing cfDNA from plasma was validated using two different approaches – digital droplet PCR and next-generation sequencing by Guardant Health.  Sequencing of cfDNA was also compared in pretreatment and post-progression samples, and novel mutations in MEK1 and GNAS were observed uniquely in post-progression samples.

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Some Carotenoids May Have a Protective Effect on Breast Cancer

MedicalResearch.com Interview with:
Ying Wang, PHD | Senior Epidemiologist
American Cancer Society, Inc.
Atlanta, Georgia

Dr. Wang: Several epidemiologic studies and a recent large pooled analysis suggest that higher blood levels of carotenoids, a group of lipid-soluble pigments that are rich in colorful fruits and vegetables, are associated with lower breast cancer risk. What remains unclear is whether or not the effect of carotenoids on breast cancer differ by estrogen receptor status, tumor stage, BMI, and smoking status. We examined plasma carotenoids and breast cancer risk overall, and by aforementioned tumor and participant characteristics in a cohort of 992 postmenopausal women. We found that higher pre-diagnosis plasma α-carotene, but not other subtypes or total carotenoids, was significantly associated with lower invasive breast cancer risk. The inverse association of α-carotene with breast cancer risk seems stronger for estrogen receptor positive tumors than for estrogen receptor negative tumors. There is a suggestive inverse association of total plasma carotenoid levels and breast cancer among ever smokers but not among never smokers.

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Novel Combination Treatment May Help Some Patients With Ovarian and Triple-negative Breast Cancers

Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer InstituteMedicalResearch.com interview with
Dr. Victoria L. Chiou, MD

Medical Oncology Fellow
Women’s Malignancies Branch
National Cancer Institute

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers.

We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population. Continue reading

HPV Vaccine Still Valuable For Women Who Were Not Fully Vaccinated As Children

Jacqueline Hirth, PhD, MPH Assistant Professor andMedicalResearch.com Interview with:
Jacqueline Hirth, PhD, MPH
Assistant Professor and
Dr. Abbey B. Berenson MD, MMS, PhD Center for Interdisciplinary Research in Women's Health Obstetrics and Gynecology The University of Texas Medical Branch at Galveston TexasDr. Abbey B. Berenson MD, MMS, PhD
Center for Interdisciplinary Research in Women’s Health
Obstetrics and Gynecology
The University of Texas Medical Branch at Galveston Texas

Medical Research: What is the background for this study? What are the main findings?

Response: In this sample of young women, vaccination was effective at reducing prevalence of vaccine-type HPV (6,11,16,18) compared to women who were unvaccinated. We also found a dose response, with young women who received at least 2 doses of the 3 dose vaccine series having a lower rate of vaccine-type HPV compared to those who only received one dose (8.6% compared to 16.9%, respectively).

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Neuropeptide Level May Signal Neuroblastoma Prognosis

MedicalResearch.com Interview with:
Joanna Kitlinska, PhD
Assistant Professor
Georgetown University Medical Center
Department of Biochemistry and Molecular & Cellular Biology
Washington, DC 20057

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Kitlinska: Neuroblastoma is a pediatric malignancy with extremely heterogeneous phenotypes, ranging from spontaneously regressing to aggressive, untreatable tumors. Consequently, treatment strategies vary significantly between patients, depending on the initial risk assessment. Given the severe late effects of anti-cancer treatment administered to infants and children, proper disease stratification is of utmost importance for neuroblastoma patients.

Due to their neuronal origin, neuroblastomas secrete neuropeptide Y (NPY), a small protein normally released from mature nerves. This, in turn, may result in elevated NPY levels in blood of neuroblastoma patients. We have found that serum NPY is particularly high in patients with aggressive, metastatic disease. Consequently, patients with elevated NPY levels have significantly worse survival. This finding is in agreement with our previous data indicating crucial role for NPY in stimulation of neuroblastoma tumor growth.

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Neuroblastoma Risk May Be Increased by Stress During Pregnancy

MedicalResearch.com Interview with:
Joanna Kitlinska, PhD
Assistant Professor
Georgetown University Medical Center
Department of Biochemistry and Molecular & Cellular Biology
Washington, DC 20057

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Kitlinska: Neuroblastoma is a pediatric tumor which arises due to defects in normal fetal neuronal development. Although the disease is associated with genetic changes, there are also clinical and experimental data implicating non-genetic factors in its etiology. We hypothesized that maternal stress during pregnancy can be one such factor, as it leads to fetal hypoxia and elevated cortisol levels – the two factors known to alter normal neuronal development and increase aggressiveness of neuroblastoma. Indeed, using an animal model of neuroblastoma, we have found that offspring of mothers which have been subjected to stress during pregnancy develop tumors twice as frequently as those from intact pregnancies. Moreover, tumors developing in prenatally-stressed mice were spreading more often to distant organs.

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HPV Vaccine Provides Protection at Multiple Sites

Daniel C. Beachler, PhD, Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) MedicalResearch.com Interview with:
Daniel C. Beachler, PhD
Postdoctoral fellow
Infections and Immunoepidemiology Branch of the
National Cancer Institute (NCI)

Medical Research: What is the background for this study? What are the main findings?

Dr. Beachler: HPV is a common sexually transmitted infection. Individuals can acquire HPV infections in the epithelium of their cervical, anal and oral sites, and occasionally these infections lead to cancer. There are three prophylactic HPV vaccines on the market that can protect against HPV at these sites among those not been previously exposed to HPV.
This study examined the effect of HPV vaccination of 18-25 year old women at all three anatomic sites. The combined multi-site HPV vaccine efficacy has not been reported previously. It was unknown whether the vaccine may protect non-infected sites against HPV infection or re-infection in women exposed to HPV prior to vaccination.
We observed that the HPV vaccine provides the strongest protection at all three sites among women unexposed to HPV before vaccination. Additionally, we observed some protection at the non-infected sites in women who were previously infected with HPV.

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PIM Kinase Inhibitors May Offer New Melanoma Therapeutic Target

Adina Vultur, Ph.D. Staff Scientist Meenhard Herlyn Laboratory Melanoma Research Center The Wistar Institute, PhiladelphiaMedicalResearch.com Interview with:
Adina Vultur, Ph.D.
Staff Scientist
Meenhard Herlyn Laboratory
Melanoma Research Center
The Wistar Institute, Philadelphia

Medical Research: What is the background for this study? What are the main findings?

Dr. Vulture: Our goal was to identify new drugs with anti-melanoma activity but with minor effects on normal cells. We screened structurally distinct kinase inhibitors first, against multiple cell lines and normal cells, and identified the organometallic compound SM200 as being the most effective and selective molecule, capable of halting melanoma cell growth and invasion. Further characterization of SM200 indicated that PIM kinases are highly inhibited by this compound compared to other targets. We then confirmed the contribution of PIM kinases to melanoma pathobiology by knockdown studies and by using a clinically available PIM-inhibitor. Encouraging results with PIM kinase inhibition in multiple melanoma models including xenografts suggests that this could be a useful strategy against melanoma.

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Some Periodontal Bacteria May Be Cancer-Promoting

Xiaodan Mai MBBS University at Buffalo, The State University of New York Buffalo, NYMedicalResearch.com Interview with:
Xiaodan Mai MBBS
University at Buffalo, The State University of New York
Buffalo, NY

MedicalResearch: What is the background for this study? What are the main findings?

Response: Periodontal disease is a condition that is highly prevalent amongst the elderly, and is characterized by chronic polymicrobial infection and inflammation of gum tissue. Periodontal disease has been associated with increased cancer risk, and these findings may be partially explained by extra-oral translocation of subgingival bacteria that subsequently modulates host cell environment and function. However, there is limited research on whether the presence of certain subgingival bacteria influences cancer risk. .

Oral bacteria have been categorized into color-coded complexes by their timing of colonization and strength of association with periodontal disease. Using data from an ancillary study of the Women’s Health Initiative conducted in Buffalo, New York (a cohort of 1300 postmenopausal women), we therefore investigated the associations between the presence of three early-colonizing periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus, i.e., “orange complex” bacteria moderately associated with PD), the presence of two late-colonizing periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, i.e., “red complex” bacteria strongly associated with PD) in dental plaque and cancer risk. We found borderline associations between presence of any early-colonizing pathogens and increased risk of total cancer and lung cancer. Individual pathogens were not associated with total cancer or site-specific cancers when analyzed singly. Presence of any pathogens or presence of any late-colonizing pathogens was not associated with total or site-specific cancer.

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