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Review Article 06 September Previous nanomedicine approaches have attempted to concentrate the action of cytotoxic therapies at tumours, generally with limited success. This Review discusses how the field is evolving to use nanoparticles and biomaterials to program the location, pharmacokinetics and co-delivery of immunotherapies, eliciting responses that cannot be achieved upon administration of such compounds in solution.

Review Article 28 August Innate immune checkpoints, including those regulating tumour detection and phagocytosis, have emerged as potential cancer immunotherapy targets. This Review discusses the role of phagocytosis checkpoints in cancer immune evasion, highlighting the preclinical and early clinical evidence supporting phagocytosis checkpoint blockade. Research Highlight 16 September Rivadeneira et al. Vaccinia -mediated engineered expression of leptin in cancer cells improved responses through metabolic reprogramming of T cells.

Research Highlight 06 September In a study published in Cell , Dong et al.

Editorial 05 September Beyond the laboratory bench, cancer researchers will face big challenges during their careers. Research Highlight 05 September Zheng et al. This strategy was able to suppress tumour growth in mouse models of colorectal cancer. Research Highlight 30 August Boettcher et al. In a study published in Cell , Riquelme et al.

Merritt Hawkins. Duke University. Fred Hutchinson Cancer Research Center. Pine Ave. USA, United States. Advanced search. Skip to main content. Comment 28 June Of scientists and tweets The use of social media for the dissemination of published and unpublished scientific findings has exploded over the past few years. Comment 01 July Preclinical rare cancer research to inform clinical trial design This Comment article argues that the future successes of rare cancer research will require alternative approaches for diagnosing, researching and conducting clinical trials, which will ultimately benefit patients with all types of cancer.

Search Nature Reviews Cancer. Latest Reviews Perspective 17 September A framework for examining how diet impacts tumour metabolism This Opinion discusses the effects of dietary factors on tumour growth and progression through changes in nutrient availability and metabolism, proposing an experimental framework for the investigation of the connections between diet and tumour metabolism. Review Article 13 September Cancer biology as revealed by the research autopsy The research autopsy is an underused approach to investigate fundamental questions in cancer biology.

Review Article 12 September Methionine metabolism in health and cancer: a nexus of diet and precision medicine Methionine uptake and metabolism contributes to cancer pathogenesis through functions in methylation reactions and one-carbon metabolism. Review Article 11 September Targeting transcription factors in cancer — from undruggable to reality This Review discusses the various approaches that are being explored to target transcription factors in cancer, with many of the inhibitors developed from such approaches now advancing to early clinical trials.

Review Article 06 September Improving cancer immunotherapy through nanotechnology Previous nanomedicine approaches have attempted to concentrate the action of cytotoxic therapies at tumours, generally with limited success. Review Article 28 August Phagocytosis checkpoints as new targets for cancer immunotherapy Innate immune checkpoints, including those regulating tumour detection and phagocytosis, have emerged as potential cancer immunotherapy targets.

More Reviews More Reviews. The initial results, presented at the San Antonio Breast Cancer Symposium, showed no statistical difference in pfs or os for the tnbc group 3. The objective response rate was also significantly higher Interestingly, on subgroup analysis of basal-like malignancies by immunohistochemistry, no statistical difference in the overall response rate was evident between the two treatment arms. The treatment of BRCA mutation—associated breast cancer and the use of directed agents for that patient subset is an active area of research.

Because the BRCA1 and BRCA2 genes code for proteins involved in double-stranded dna break repair, it is hypothesized that BRCA mutation—associated cancers might be more sensitive to chemotherapy agents that cause dna damage, such as the platinums.

Physiotherapy and cancer treatment

Sensitivity of that kind has been shown in vitro 42 ; however, its translation into clinical application has yet to be established. However, the study lacked a control group. That activity has been confirmed by in vitro studies, showing that tumours in carriers are in fact sensitive to parp inhibitors 45 , Recently, the parp inhibitor olaparib was studied in the setting of metastatic breast cancer in the o lympi ad trial That study included patients with metastatic breast cancer who had known BRCA mutations, who were negative for her 2 overexpression, and who had received up to 2 prior lines of chemotherapy.

The patients were randomized to single-agent chemotherapy capecitabine, eribulin, or vinorelbine every 3 weeks or to olaparib mg twice daily. The response rate was Furthermore, pfs was improved in the olaparib group 7.


Olaparib was approved in January by the U. In Canada, olaparib is currently approved for use only in BRCA -mutated ovarian, fallopian tube, or primary peritoneal cancers. Other parp inhibitors are also actively being investigated in the metastatic setting, including veliparib and niraparib for example, NCT, NCT The angiogenesis inhibitor bevacizumab has been examined in combination with chemotherapy agents in the treatment of metastatic breast cancer 49 , Although the relevant studies demonstrated benefit in pfs , no improvement in os was observed.

Miles et al. In the tnbc subgroup, median pfs was significantly improved with the use of bevacizumab hr : 0. Thus, no role for bevacizumab is accepted at this time. The role of immunotherapy in the treatment of tnbc is currently under investigation in several trials recruiting in Canada Table ii.

In tnbc , strong lymphocytic infiltration or immune response has been associated with improved prognosis That observation suggests that harnessing the immune system against this disease might be beneficial. Pembrolizumab is a PD-1 inhibitor that has been shown to be effective in the treatment of several other cancers, including lung, melanoma, and bladder malignancies 53 — In a phase ib study of pembrolizumab in patients with advanced tnbc , only Immunotherapy has shown great potential in a number of other disease sites, and thus the results of the foregoing trials are highly anticipated.

EMBL - European Molecular Biology Laboratory

In a subgroup of tnbc , expression of the androgen receptor ar is increased The clinical relevance of ar status has yet to be established in breast cancer; however, several recent phase ii studies have examined the use of anti-androgen agents in this setting. In one study, tumours from patients with breast cancer negative for the estrogen and progesterone receptors were tested for ar expression Patients whose tumours tested positive received bicalutamide mg daily.

A phase iii evaluation of bicalutamide is still pending. Enzalutamide is an ar signalling inhibitor that is used in the treatment of metastatic castration-resistant prostate cancer. The effect of enzalutamide has also been studied in ar -positive tnbc in a phase ii trial Additionally, median pfs was 32 weeks compared with 9 weeks for patients testing negative. Triple-negative breast cancer constitutes a heterogeneous group of malignancies that differ in natural history and response to treatment. The mainstay of treatment continues to be chemotherapy; however, optimal chemotherapy regimens for tnbc have yet to be established.


In this article, we have reviewed the current evidence for systemic treatment for tnbc in the neoadjuvant, adjuvant, and metastatic settings. In the neoadjuvant setting, the use of platinum agents has been associated with improved rates of p cr , but os was not reported in the associated studies 30 , In the recently published create - x trial, an os benefit was shown for adjuvant capecitabine in patients who do not achieve a p cr with neoadjuvant chemotherapy However, that approach has not been widely adopted in clinical practice, perhaps because of the associated toxicity.

For adjuvant treatment of tnbc , two trials that added weekly paclitaxel to combination chemotherapy showed improvements in dfs 33 — In metastatic tnbc , preliminary results show that the response rate might be higher with platinum than with docetaxel in BRCA mutation—associated malignancies 40 ; however, research to guide the optimal choice of systemic treatment for metastatic disease is limited.

Olaparib, a parp inhibitor, has recently been approved by the U. Food and Drug Administration for use in germline BRCA -mutated metastatic breast cancer, based on the o lympi ad trial As molecular research advances an understanding of the driver mutations in this disease, more targeted treatments could become available. A number of investigational therapies hold promise, including parp inhibitors, ar pathway inhibitors, and immunotherapy.

Given those new developments, the hope is that more effective treatments and better outcomes will be achieved for patients with tnbc. MS has received conference funding from Amgen and fees as an advisory board member for Pfizer and Shire. JM has received conference travel funding from AstraZeneca and Roche and fees as an advisory board member from Novartis and Pfizer.

Nature Reviews Cancer

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Incidence and outcome of BRCA mutations in unselected patients with triple receptor—negative breast cancer. Clin Cancer Res ;—9.

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National Comprehensive Cancer Network nccn. Fort Washington, PA: nccn ; Primary breast cancer: esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol ;26 suppl 5 :v8— Optimal systemic therapy for early breast cancer in women: a clinical practice guideline. Curr Oncol ;22 sup-pl 1 :S67— Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 her 2 —negative and adjuvant targeted therapy for her 2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline.

Ann Oncol ;— Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2—negative or unknown advanced breast cancer: American Society of Clinical Oncology clinical practice guideline. How basal are triple-negative breast cancers? Int J Cancer ;— Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.

An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol ;8:R Repeated observation of breast tumor subtypes in independent gene expression data sets. Nat Rev Cancer ;— Locoregional therapy of locally advanced breast cancer: a clinical practice guideline.

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Curr Oncol ;S54— Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer.

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