Blogger's Note: 1 reference to ovarian cancer - "Genetic determinants of human health and disease (including breast, endometrial, prostate, ovarian and melanoma cancers)."
Report Card
Tuesday, April 07, 2015
Report Card - Reflections on 2014 (Canada) Cancer Advocacy Coalition
Blogger's Note: 1 reference to ovarian cancer - "Genetic determinants of human health and disease (including breast, endometrial, prostate, ovarian and melanoma cancers)."
Report Card
Ovarian Sex Cord-Stromal Tumors in Patients With Probable or Confirmed Germline DICER1 Mutations
Oabstract
....The present small series suggests that some ovarian Sertoli-Leydig cell tumor associated with germline DICER1 mutations may show distinctive histologic features in particular admixed Sertoli cell and juvenile granulosa cell tumor-like features. Larger studies are required to establish whether heterologous elements are also a more common feature of these tumors.
Cediranib Aims for a Comeback
extract JNCI
Women with advanced ovarian or cervical cancer are living longer, with fewer disease symptoms, and that reflects advances
across clinical and supportive therapies.
Bevacizumab, for instance—a
recently approved monoclonal antibody that targets vascular endothelial
growth factor (VEGF)—improves
overall survival (OS) and progression-free survival
(PFS) in both diseases. In August 2014, the U.S. Food and Drug
Administration
approved bevacizumab in combination with
chemotherapy to treat platinum-resistant recurrent ovarian cancer. And
the following
November, FDA approved the drug to treat
persistent, recurrent, or metastatic cervical cancer, also with
chemotherapy. Those
were the first new approvals in ovarian and
cervical cancer treatment since 2006.
Interest Revived
Now a different VEGF-directed compound,
cediranib, a tyrosine kinase inhibitor, is making steady gains in
ovarian and cervical
cancer treatment. Cediranib’s manufacturer,
AstraZeneca, abandoned its own sponsored development of the drug in 2011
after
it failed to meet phase III goals in lung and
colorectal cancers. But investigator-initiated studies in gynecological
cancers
gave cediranib another chance. These studies
show improved OS and PFS, but also with side effects that seem worse
than those
associated with bevacizumab, according to David
Hyman, M.D., a gynecological medical oncologist and assistant professor
at
New York’s Memorial Sloan–Kettering Cancer
Center.
“We don’t really know if bevacizumab and cediranib are interchangeable,” he said. “We still need to define the approval setting
…
Breast Cancer Patients Concerned About Genetic Risk, Survey Finds
Drugs.com
MONDAY April 6, 2015, 2015 -- Although many women with breast cancer are concerned about their genetic risk for other cancers -- as well as their relatives' risk for breast cancer -- almost half of these patients don't get information about genetic testing, a new study finds.
Researchers surveyed more than 1,500 breast cancer patients in Detroit and Los Angeles and found that 35 percent had a strong interest in genetic testing.......Many of those interested in genetic testing were also concerned about their own future risk of other types of cancer, according to the study in the current issue of the Journal of Clinical Oncology....
Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future
abstract
Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that prevents administration of the full efficacious dosage and often leads to treatment withdrawal. Peripheral sensory neurotoxicity varies from paresthesia in fingers to ataxic gait, which might be transient or irreversible. Because the number of patients being treated with these neurotoxic agents is still increasing, the need for understanding the pathogenesis of this dramatic side effect is critical. Platinum derivatives, such as cisplatin and carboplatin, harm mainly peripheral nerves and dorsal root ganglia neurons, possibly because of progressive DNA-adduct accumulation and inhibition of DNA repair pathways (e.g., extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 mitogen-activated protein kinass), which finally mediate apoptosis. Oxaliplatin, with a completely different pharmacokinetic profile, may also alter calcium-sensitive voltage-gated sodium channel kinetics through a calcium ion immobilization by oxalate residue as a calcium chelator and cause acute neurotoxicity. Polymorphisms in several genes, such as voltage-gated sodium channel genes or genes affecting the activity of pivotal metal transporters (e.g., organic cation transporters, organic cation/carnitine transporters, and some metal transporters, such as the copper transporters, and multidrug resistance-associated proteins), can also influence drug neurotoxicity and treatment response. However, most pharmacogenetics studies need to be elucidated by robust evidence. There are supportive reports about the effectiveness of several neuroprotective agents (e.g., vitamin E, glutathione, amifostine, xaliproden, and venlafaxine), but dose adjustment and/or drug withdrawal seem to be the most frequently used methods in the management of platinum-induced peripheral neurotoxicity. To develop alternative options in the treatment of platinum-induced neuropathy, studies on in vitro models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution.
BRCA1 and BRCA2 Mutations in Ethnic Lebanese Arab Women With High Hereditary Risk Breast Cancer
abstract
Conclusion. Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended.
Monday, April 06, 2015
A targeted analysis identifies a high frequency of BRCA1 & 2 mutation carriers in women with ovarian cancer from a founder population
Journal of Ovarian Research | Full text | A targeted analysis identifies a high frequency of BRCA1 and BRCA2 mutation carriers in women with ovarian cancer from a founder population
Background
The frequency of BRCA1 and BRCA2 mutations in ovarian cancer patients varies depending on histological subtype and population investigated. The six most commonly recurring BRCA1 and BRCA2 mutations previously identified in a founder French Canadian population were investigated in 439 histologically defined ovarian, fallopian tube and primary peritoneal cancer cases that were ascertained at one hospital servicing French Canadians. To further assess the frequency of BRCA1/BRCA2 mutations, a defined subgroup of 116 cases were investigated for all mutations previously reported in this population.....
http://ovariancancerandus.blogspot.com/feeds/posts/default
Ovarian, fallopian tube and peritoneal cancer staging: rationale and explanation of new FIGO staging 2013
abstract
Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture (“surgical spill”) is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB).
Relationship of tumor marker CA125 and ovarian tumor stem cells
Full text: Relationship of tumor marker CA125 and ovarian tumor stem cells: preliminary identification
....In 1981, Robert et al. [18] found antigen CA125 in the ovarian cancer cells by using monoclonal antibody OC125. Since then, CA125 has been an auxiliary diagnostic marker for ovarian cancer, and research about immunological treatment of ovarian cancer using the antibody’s specificity for CA125 is also emerging. Our experiments showed that CA125 may be one of the surface markers of tumor stem cells, and further studies are needed to investigate the existence of other markers, which is the direction of our future studies. Finding the markers of ovarian cancer stem cells and targeting killing these “seed cells”, making the prevention and treatment of ovarian cancer possible.
Evidence for induction of a tumor metastasis-receptive microenvironment for ovarian cancer cells in bone marrow and other organs as an unwanted and underestimated side effect of chemotherapy/radiotherapy
Journal of Ovarian Research - open access
Background One of side effects of chemotherapy and radiotherapy is the induction of
several factors in various tissues and organs that create a pro-metastatic microenvironment
for cancer cells that survive initial treatment. Methods In the present study, we
employed human ovarian cancer cell line A2780 and immunodeficient mice xenogrfat model
to test effect of both ibuprofen and dexamethasone to ameliorate the therapy-induced
pro-metastatic microenvironment in bone marrow, liver, and lung. Results In our studies,
we found that total body irradiation or administration of cisplatin increases the
metastatic spread of human ovarian cancer cells transplanted into immunodeficient
mice compared with animals unexposed to irradiation or cisplatin. Moreover, conditioned
media harvested from irradiated murine bone marrow, lung, and liver chemoattracted
human ovarian cancer cells, and this chemotactic activity was inactivated by heat,
suggesting a major involvement of peptide or peptide-bound chemoattractants. We also
observed that human ovarian cancer cells proliferate better if exposed to cell debris
harvested from irradiated murine bone marrow. Finally, the pro-metastatic microenvironment
in mice induced by radio- or chemotherapy was significantly ameliorated if animals
were treated at the time of radiochemotherapy administration with non-steroid (ibuprofen)
or steroid (prednisone) anti-inflammatory drugs. Conclusions In summary, we propose
that a radiochemotherapy-induced, pro-metastatic microenvironment plays an important
role in the metastasis of cancer cells that are resistant to treatment. Such cells
have characteristics of cancer stem cells and are highly migratory, and simple, intensive,
anti-inflammatory treatment by non-steroid agents to suppress induction of pro-metastatic
factors after radiochemotherapy would be an interesting anti-metastatic treatment
alternative.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
open access: Development and analytical validation of a 25-gene next generation sequencing panel that includes the BRCA1 & 2 genes to assess hereditary cancer risk
open access - authors Myriad
Background Germline DNA mutations that increase the susceptibility of a patient to certain cancers have been identified in various genes, and patients can be screened for mutations in these genes to assess their level of risk for developing cancer. Traditional methods using Sanger sequencing focus on small groups of genes and therefore are unable to screen for numerous genes from several patients simultaneously. The goal of the present study was to validate a 25-gene panel to assess genetic risk for cancer in 8 different tissues using next generation sequencing (NGS) techniques. Methods Twenty-five genes associated with hereditary cancer syndromes were selected for development of a panel to screen for risk of these cancers using NGS. In an initial technical assessment, NGS results for BRCA1 and BRCA2 were compared with Sanger sequencing in 1864 anonymized DNA samples from patients who had undergone previous clinical testing. Next, the entire gene panel was validated using parallel NGS and Sanger sequencing in 100 anonymized DNA samples. Large rearrangement analysis was validated using NGS, microarray comparative genomic hybridization (CGH), and multiplex ligation-dependent probe amplification analyses (MLPA). Results NGS identified 15,877 sequence variants, while Sanger sequencing identified 15,878 in the BRCA1 and BRCA2 comparison study of the same regions. Based on these results, the NGS process was refined prior to the validation of the full gene panel. In the validation study, NGS and Sanger sequencing were 100% concordant for the 3,923 collective variants across all genes for an analytical sensitivity of the NGS assay of >99.92% (lower limit of 95% confidence interval). NGS, microarray CGH and MLPA correctly identified all expected positive and negative large rearrangement results for the 25-gene panel. Conclusion This study provides a thorough validation of the 25-gene NGS panel and indicates that this analysis tool can be used to collect clinically significant information related to risk of developing hereditary cancers.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Tackling the cancer epidemic - Editorial
The Lancet Oncology
Editorial
Tackling the cancer epidemic
Cancer
is the primary cause of death in many countries, now exceeding heart
disease. In lower income countries, incidence is rising fast, creating
unprecedented challenges for health systems, many of which were designed
in an era that did not foresee, were simply incapable of pre-empting,
or knowingly ignored the future. For lower-to-middle income countries,
these challenges are multiplied by the double burden of disease—the
long-running battle against infection complicated by the rising burden
of chronic diseases.
Advances in care are allowing
patients to live longer, better quality lives. Survival has improved
substantially as knowledge of the biology and aetiology of cancer has
increased, offering the promise of precision oncology. However, these
remarkable achievements come at a price—the cost of care is outpacing
national budgets, the numbers of cancer patients and survivors are
putting greater pressures on health-care systems, and increasing numbers
of vulnerable patients from less traditional demographics, such as
children and younger adults, require different clinical solutions that
have yet to be fully conceived.
This month, The Lancet Oncology launches a campaign
focused on tackling the cancer epidemic at a systems level. This
campaign will provide a comprehensive assessment of the necessary
changes in patient services and outcomes. We will document, via monthly
updates, the evolution of four Commissions intended for publication
later this year that aim to define the scale of the challenge, the
underlying drivers, and the improvements needed to cancer-care systems.
These special reports will cover global access to radiotherapy, surgical
resource availability and its fundamental role in cancer treatment, the
intersection of primary care in a comprehensive cancer service fit for
the 21st century, and the ongoing oncology requirements in the
low-to-middle income countries of Latin America. When published, we hope
these Commissions will offer practical advice and specific
recommendations to help overcome this tremendous health-care challenge.
Ovarian Cancer National Alliance - 2015 report SGO conference
American Gastroenterological Association technical review on diagnosis and management of Lynch syndrome
pdf (81 pages)
reference:
16.National Comprehensive Cancer Network, About the NCCN Clinical Practice Guidelines in Oncology. 2014. (Accessed Januaty 2015, at https://www.nccn.org/store/login/login.aspx?ReturnURL=http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.)
Ovarian Cancer - CRI
CRI
.... A number of immune-based therapies are being investigated in early-phase clinical trials for patients with ovarian cancer. Go to our Cancer Immunotherapy Clinical Trial Finder to find clinical trials of immunotherapies for ovarian cancer that are currently enrolling patients.....
A
number of immune-based therapies are being investigated in early-phase
clinical trials for patients with ovarian cancer. Go to our Cancer
Immunotherapy Clinical Trial Finder to find clinical trials of
immunotherapies for ovarian cancer that are currently enrolling
patients. - See more at:
http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/ovarian-cancer#sthash.oremPX4Q.dpuf
A
number of immune-based therapies are being investigated in early-phase
clinical trials for patients with ovarian cancer. Go to our Cancer
Immunotherapy Clinical Trial Finder to find clinical trials of
immunotherapies for ovarian cancer that are currently enrolling
patients. - See more at:
http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/ovarian-cancer#sthash.oremPX4Q.dpuf
IMMUNOTHERAPy
Immunotherapy for Ovarian Cancer - CRI
Immunotherapy for Ovarian Cancer - CRI
Checkpoint Inhibitors and Immune Modulators
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
Ipilimumab (Yervoy®), which targets the CTLA-4 checkpoint molecule on activated immune cells, is being tested in a variety of cancer types, including ovarian cancer, for which a phase II study (NCT01611558) is currently under way.
MEDI4736, an anti-PD-L1 checkpoint inhibitor made by MedImmune/AstraZeneca, is being tested in a number of trials:
A phase I/II trial of MEDI4736 for patients with solid tumors (NCT01693562).
A phase I/II trial of MEDI6469, an anti-OX40 agonist antibody, alone or with tremelimumab, an anti-CTLA-4 antibody, and/or MEDI4736 (NCT02205333).
A phase I trial of MEDI0680 (AMP-514), an anti-PD-1 antibody, and MEDI4736 in patients with advanced cancers (NCT02118337).
MEDI4736 and tremelimumab are being tested in two trials. One is a phase I trial sponsored by MedImmune for patients with solid tumors (NCT02261220). The other is a phase I trial, sponsored by Ludwig Cancer Research in collaboration with CRI and MedImmune, in patients with advanced solid tumors, including ovarian cancer (NCT01975831).
A phase Ib trial to test pembrolizumab (Keytruda®, MK-3475), an anti-PD-1 antibody being developed by Merck, in patients with advanced, biomarker-positive solid tumors (NCT02054806).
Two phase I trials to test MPDL3280A, an anti-PD-L1 antibody being developed by Roche/Genentech, in patients with several cancers (NCT01375842, NCT01633970).
A phase I trial testing urelumab (BMS-663513), an anti-4-1BB/CD137 antibody made by Bristol-Myers Squibb, in patients with advanced cancers (NCT01471210). Another phase I/II trial of urelumab given along with nivolumab (anti-PD-1) in patients with solid tumors (NCT02253992).
A phase I trial to test PF-05082566, an anti-4-1BB/CD137 antibody developed by Pfizer, in patients with solid tumors (NCT01307267).
A phase I study of lirilumab, an anti-KIR antibody being developed by Bristol-Myers Squibb, in combination with nivolumab (anti-PD-1) in patients with advanced solid tumors (NCT01714739).
A phase I trial to test BMS-986016, a LAG-3 antibody, with or without nivolumab (anti-PD-1) in patients with solid tumors (NCT01968109).
A pilot study to test INCB024360, an IDO1 inhibitor, in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer (NCT02042430).
Checkpoint Inhibitors and Immune Modulators
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
- Ipilimumab (Yervoy®), which targets the CTLA-4 checkpoint molecule on activated immune cells, is being tested in a variety of cancer types, including ovarian cancer, for which a phase II study (NCT01611558) is currently under way.
-
MEDI4736, an anti-PD-L1 checkpoint inhibitor made by MedImmune/AstraZeneca, is being tested in a number of trials:
- A phase I/II trial of MEDI4736 for patients with solid tumors (NCT01693562).
- A phase I/II trial of MEDI6469, an anti-OX40 agonist antibody, alone or with tremelimumab, an anti-CTLA-4 antibody, and/or MEDI4736 (NCT02205333).
- A phase I trial of MEDI0680 (AMP-514), an anti-PD-1 antibody, and MEDI4736 in patients with advanced cancers (NCT02118337).
- MEDI4736 and tremelimumab are being tested in two trials. One is a phase I trial sponsored by MedImmune for patients with solid tumors (NCT02261220). The other is a phase I trial, sponsored by Ludwig Cancer Research in collaboration with CRI and MedImmune, in patients with advanced solid tumors, including ovarian cancer (NCT01975831).
- A phase Ib trial to test pembrolizumab (Keytruda®, MK-3475), an anti-PD-1 antibody being developed by Merck, in patients with advanced, biomarker-positive solid tumors (NCT02054806).
- Two phase I trials to test MPDL3280A, an anti-PD-L1 antibody being developed by Roche/Genentech, in patients with several cancers (NCT01375842, NCT01633970).
- A phase I trial testing urelumab (BMS-663513), an anti-4-1BB/CD137 antibody made by Bristol-Myers Squibb, in patients with advanced cancers (NCT01471210). Another phase I/II trial of urelumab given along with nivolumab (anti-PD-1) in patients with solid tumors (NCT02253992).
- A phase I trial to test PF-05082566, an anti-4-1BB/CD137 antibody developed by Pfizer, in patients with solid tumors (NCT01307267).
- A phase I study of lirilumab, an anti-KIR antibody being developed by Bristol-Myers Squibb, in combination with nivolumab (anti-PD-1) in patients with advanced solid tumors (NCT01714739).
- A phase I trial to test BMS-986016, a LAG-3 antibody, with or without nivolumab (anti-PD-1) in patients with solid tumors (NCT01968109).
- A pilot study to test INCB024360, an IDO1 inhibitor, in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer (NCT02042430).
Checkpoint Inhibitors and Immune Modulators
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
- Ipilimumab (Yervoy®), which targets the CTLA-4 checkpoint molecule on activated immune cells, is being tested in a variety of cancer types, including ovarian cancer, for which a phase II study (NCT01611558) is currently under way.
-
MEDI4736, an anti-PD-L1 checkpoint inhibitor made by MedImmune/AstraZeneca, is being tested in a number of trials:
- A phase I/II trial of MEDI4736 for patients with solid tumors (NCT01693562).
- A phase I/II trial of MEDI6469, an anti-OX40 agonist antibody, alone or with tremelimumab, an anti-CTLA-4 antibody, and/or MEDI4736 (NCT02205333).
- A phase I trial of MEDI0680 (AMP-514), an anti-PD-1 antibody, and MEDI4736 in patients with advanced cancers (NCT02118337).
- MEDI4736 and tremelimumab are being tested in two trials. One is a phase I trial sponsored by MedImmune for patients with solid tumors (NCT02261220). The other is a phase I trial, sponsored by Ludwig Cancer Research in collaboration with CRI and MedImmune, in patients with advanced solid tumors, including ovarian cancer (NCT01975831).
- A phase Ib trial to test pembrolizumab (Keytruda®, MK-3475), an anti-PD-1 antibody being developed by Merck, in patients with advanced, biomarker-positive solid tumors (NCT02054806).
- Two phase I trials to test MPDL3280A, an anti-PD-L1 antibody being developed by Roche/Genentech, in patients with several cancers (NCT01375842, NCT01633970).
- A phase I trial testing urelumab (BMS-663513), an anti-4-1BB/CD137 antibody made by Bristol-Myers Squibb, in patients with advanced cancers (NCT01471210). Another phase I/II trial of urelumab given along with nivolumab (anti-PD-1) in patients with solid tumors (NCT02253992).
- A phase I trial to test PF-05082566, an anti-4-1BB/CD137 antibody developed by Pfizer, in patients with solid tumors (NCT01307267).
- A phase I study of lirilumab, an anti-KIR antibody being developed by Bristol-Myers Squibb, in combination with nivolumab (anti-PD-1) in patients with advanced solid tumors (NCT01714739).
- A phase I trial to test BMS-986016, a LAG-3 antibody, with or without nivolumab (anti-PD-1) in patients with solid tumors (NCT01968109).
- A pilot study to test INCB024360, an IDO1 inhibitor, in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer (NCT02042430).
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