Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers.

https://onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21149

Cancer treatment and survivorship statistics, 2012

Insulin and insulin-like growth factors (IGFs) are well known as key regulators of energy metabolism and growth. There is now considerable evidence that these hormones and the signal transduction networks they regulate have important roles in neoplasia. Epidermiological, clinical and laboratory research methods are being used to investigate novel cancer prevention and treatment strategies related to insulin and IGF signalling. Pharmacological strategies under study include the use of novel receptor-specific antibodies, receptor kinase inhibitors and AMP-activated protein kinase activators such as metformin. There is evidence that insulin and IGF signalling may also be relevant to dietary and lifestyle factors that influence cancer risk and cancer prognosis. Recent results are encouraging and have justified the expansion of many translational research programmes.

Insulin and insulin-like growth factor signalling in neoplasia

The vascular network delivers oxygen (O(2)) and nutrients to all cells within the body. It is therefore not surprising that O(2) availability serves as a primary regulator of this complex organ. Most transcriptional responses to low O(2) are mediated by hypoxia-inducible factors (HIFs), highly conserved transcription factors that control the expression of numerous angiogenic, metabolic, and cell cycle genes. Accordingly, the HIF pathway is currently viewed as a master regulator of angiogenesis. HIF modulation could provide therapeutic benefit for a wide array of pathologies, including cancer, ischemic heart disease, peripheral artery disease, wound healing, and neovascular eye diseases. Hypoxia promotes vessel growth by upregulating multiple pro-angiogenic pathways that mediate key aspects of endothelial, stromal, and vascular support cell biology. Interestingly, recent studies show that hypoxia influences additional aspects of angiogenesis, including vessel patterning, maturation, and function. Through extensive research, the integral role of hypoxia and HIF signaling in human disease is becoming increasingly clear. Consequently, a thorough understanding of how hypoxia regulates angiogenesis through an ever-expanding number of pathways in multiple cell types will be essential for the identification of new therapeutic targets and modalities.

http://gan.sagepub.com/content/2/12/1117.full.pdf+html

Hypoxia-Induced Angiogenesis Good and Evil

Purpose To provide evidence-based recommendations to update the American Society of Clinical Oncology guideline on systemic therapy for stage IV non–small-cell lung cancer (NSCLC). Methods An Update Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of randomized controlled trials from January 2007 to February 2014. Results This guideline update reflects changes in evidence since the previous guideline. Recommendations There is no cure for patients with stage IV NSCLC. For patients with performance status (PS) 0 to 1 (and appropriate patient cases with PS 2) and without an EGFR-sensitizing mutation or ALK gene rearrangement, combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care. Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications); combination or single-agent chemotherapy or palliative care alone for those with PS 2; afatinib, erlotinib, or gefitinib for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma. Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens, alternative chemotherapy, or a chemotherapy break. In the second-line setting, recommendations include docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma; docetaxel, erlotinib, or gefitinib for those with squamous cell carcinoma; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib. In the third-line setting, for patients who have not received erlotinib or gefitinib, treatment with erlotinib is recommended. There are insufficient data to recommend routine third-line cytotoxic therapy. Decisions regarding systemic therapy should not be made based on age alone. Additional information can be found at http://www.asco.org/guidelines/nsclc and http://www.asco.org/guidelineswiki. J Clin Oncol 33:3488-3515. © 2015 by American Society of Clinical Oncology

https://ascopubs.org/doi/pdf/10.1200/JCO.2015.62.1342

Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development. Recommendations New or revised recommendations include the following. Regarding first-line treatment for patients with non-squamous cell carcinoma or squamous cell carcinoma (without positive markers, eg, EGFR/ALK /ROS1), if the patient has high programmed death ligand 1 (PD-L1) expression, pembrolizumab should be used alone; if the patient has low PD-L1 expression, clinicians should offer standard chemotherapy. All other clinical scenarios follow 2015 recommendations. Regarding second-line treatment in patients who received first-line chemotherapy, without prior immune checkpoint therapy, if NSCLC tumor is positive for PD-L1 expression, clinicians should use single-agent nivolumab, pembrolizumab, or atezolizumab; if tumor has negative or unknown PD-L1 expression, clinicians should use nivolumab or atezolizumab. All immune checkpoint therapy is recommended alone plus in the absence of contraindications. For patients who received a prior first-line immune checkpoint inhibitor, clinicians should offer standard chemotherapy. For patients who cannot receive immune checkpoint inhibitor after chemotherapy, docetaxel is recommended; in patients with nonsquamous NSCLC, pemetrexed is recommended. In patients with a sensitizing EGFR mutation, disease progression after first-line epidermal growth factor receptor tyrosine kinase inhibitor therapy, and T790M mutation, osimertinib is recommended; if NSCLC lacks the T790M mutation, then chemotherapy is recommended. Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib, or if they previously received crizotinib, they may be offered chemotherapy.

/pdf/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-wjyt4bbmlb.pdf

Breast Cancer Testing Scandal Shines Spotlight on Black Box of Clinical Laboratory Testing

Cancer patients know that chemobrain is real. The nearly ubiquitous experience of foggy thinking immediately after chemotherapy treatment has even inspired T-shirts and buttons emblazoned with “My Name is Chemo Brain.” For some cancer survivors, the cognitive effects of chemotherapy such as lack of concentration and short-term memory loss linger for years after treatment, but little is known about who is most likely to suffer a long-term

Chemobrain Is Real but May Need New Name

and proprietary issues that have hampered efforts to share data. He developed Project Data Sphere, which within weeks will go live with cancer trial data from an expected five to seven pharmaceutical companies. The goal, according to Hugh-Jones, is to have Project Data Sphere grow into an interactive platform where investigators can learn from the collective successes and failures of previous trials with the help of powerful analytic tools, which the statistical software giant SAS Institute offered to the project free. “The reality is that we have to do better,” said Hugh-Jones. “You’ve got to get beyond a 5% success rate in bringing new oncology drugs to market. But it’s an economic issue as well. People are realizing there just isn’t the money to keep pumping into trials either at a commercial or at a governmental level.”

Project Data Sphere To Make Cancer Clinical Trial Data Publicly Available

/pdf/research-groups-promoting-proton-therapy-lite-3wefcuea0w.pdf

Research Groups Promoting Proton Therapy “Lite”

The discovery of RNA interference (RNAi), the endogenous regulatory system that employs small doublestranded RNA molecules to silence gene expression, has generated enthusiasm for using small interfering RNA – based molecules (siRNA) to treat a variety of diseases. It didn’t take long for investigators to dream up several strategies for siRNA to target cancer. And recent studies offer tantalizing clues that RNAi is not only a potential therapeutic measure—it can also act as an intrinsic part of the oncogenic process. Some of the enthusiasm surrounding RNAi is based on the assumption that since RNAi taps into a fundamental regulatory process, it should be well tolerated and generate few side effects. “RNAi works by tapping into a natural process that has evolved to regulate gene expression,” said Cold Spring Harbor Laboratory’s Greg Hannon, Ph.D., a pioneer in RNAi. “The cells use this already; all we are doing is altering the programming. We are not trying to force a cell to do something that it normally doesn’t do. With RNAi you have an entire machinery that has evolved to fi nd complementary targets. ... I think that in the end we are going to fi nd that tapping into this natural mechanism is going to be a lot more effective [than other types of nucleic acid – based therapy].” Since it was fi rst discovered in the late 1990s, investigators have made much progress in understanding how eukaryotic cells use small doublestranded RNAs to regulate gene expression. In back-to-back papers published in the February issue of Nature Biotechnology , John Rossi, Ph.D., at the City of Hope in Duarte, Calif., and his group and Hannon’s group described how to design siRNA templates that effectively activate a group of proteins called the RNAinduced silencing complex (RISC), whose activation results in sequence-specifi c gene silencing. “We now have 75% or 80% of the equation for making a pretty good siRNA,” said Hannon. “The more natural your trigger becomes, the more effectively it is incorporated in the RISC complex.”

Blocking Cancer With RNA Interference Moves Toward the Clinic

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