AACR, Author Interviews, Breast Cancer, UCSD / 21.04.2015

Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New YorMedicalResearch.com Interview with: Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New York Medical Research: What is the background for this study? This year, breast cancer will claim the lives of nearly 40,000 women in the United States, and up to half of these women will have a disease that is driven by the estrogen receptor.
  • Although medicines have been approved for the treatment of hormone receptor-positive breast cancer for decades, more treatment options are needed.
  • Resistance to endocrine therapies causes morbidity and mortality for women with metastatic estrogen receptor-positive (ER+) breast cancer as many patients relapse or develop resistance to available hormonal agents via estrogen-dependent and estrogen-independent mechanisms.
  • Dual-acting investigational Selective Estrogen Receptor Degrader (SERDs) could potentially lead to a new treatment option for people with hormone receptor-positive breast cancer and may help overcome resistance to current anti-hormonal medicines.
  • GDC-0810 is a dual-acting investigational next-generation oral SERD that works in a number of ways to prevent estrogen fueling tumor growth. It is not only designed to target the estrogen receptor (ER) as an antagonist, but also to cause degradation of the ER protein. In preclinical studies, GDC-0810 was shown to induce tumor regressions in both tamoxifen sensitive and tamoxifen resistant tumor models in vivo.
Medical Research: What are the main findings?
  • Clinical data from the dose-escalation portion of a Phase I/IIa study evaluating GDC-0810 appears to have an acceptable safety profile with encouraging anti-tumor activity in postmenopausal women with advanced breast cancer positive for the estrogen receptor (ER), all of whom were previously treated with standard endocrine therapy.
  • Promising anti-tumor activity was observed in 38% of patients on study for six months or longer. At all doses tested, there was robust engagement of the estrogen receptor by GDC-0810 as demonstrated by fluoroestradiol (FES) PET scans.  Overall, the most common adverse events of any grade related to GDC-0810 were diarrhea, nausea and fatigue.
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AACR, Author Interviews, Cancer Research / 20.04.2015

Presented by Dr. Jeffrey R. Infante, MD 2015 American Association for Cancer Research Director of the Drug Development Program Sarah Cannon Research Institute in Nashville, Tennessee.MedicalResearch.com Interview with: Presented by Dr. Jeffrey R. Infante, MD 2015 American Association for Cancer Research Director of the Drug Development Program Sarah Cannon Research Institute in Nashville, Tennessee. Medical Research: What is the background for this study?
  • Inhibition of Checkpoint Kinase 1 (Chk1) may be effective at enhancing the effects of chemotherapeutic agents in tumor cells that lack other key cell cycle checkpoint regulators, such as the tumor suppressor protein p53 (p53 mutant tumors).
  • In a broad range of pre-clinical models, GDC-0425, an oral, selective Chk1 inhibitor, enhanced the efficacy of the chemotherapy drug gemcitabine. Greater efficacy was also observed in cancer cell lines lacking p53 activity.
  • Based on its proposed mechanism of action in enhancing the cytotoxicity of DNA damaging chemotherapy, GDC-0425 was evaluated in combination with a standard dose of gemcitabine.
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AACR, Author Interviews, Melanoma, Wistar / 20.04.2015

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. (more…)
AACR, Author Interviews, Cancer Research, Dental Research, Microbiome / 20.04.2015

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. (more…)
AACR, Author Interviews, Breast Cancer, Nutrition, UCSD / 20.04.2015

Catherine Marinac Doctoral Candidate UC San Diego/San Diego State University Joint-Doctoral Program in Public Health La Jolla, CA 92093MedicalResearch.com Interview with: Catherine Marinac Doctoral Candidate UC San Diego/San Diego State University Joint-Doctoral Program in Public Health La Jolla, CA 92093 MedicalResearch: What is the background for this study? What are the main findings? Response: The dietary advice for cancer prevention usually focuses on limiting consumption of red meat, alcohol, and refined grains, and increasing consumption of plant foods. However, new evidence suggests that other fundamental aspects of diet, such when and how often people eat, can also play a role in cancer risk. For example, research in mice suggests that decreasing the number of hours we eat during the day, and increasing the length of time we fast overnight can improve metabolic parameters and reduce risk of developing a number of chronic diseases including cancer. Similar to the data from animal models, we found that women who fasted for longer periods of time overnight had significantly better control over blood glucose concentrations – and these effects were independent of how much women ate. This finding is relevant to cancer research because people who have poor glucose control are significantly more likely to develop certain types of cancer. It is hypothesized that high concentrations of circulating glucose may fuel cancer growth and progression. (more…)