What's new?

Microtubule affinity-regulating kinases (MARKs) have been implicated in multiple cellular processes, including intracellular transport, cell polarity, and cell migration. Yet, few studies have correlated MARK kinase expression with cancer, and none have explored their role in lung cancer. Here, the authors describe for the first time highly frequent DNA and RNA-level disruption of MARK2 in clinical non-small cell lung cancer (NSCLC) cases. They provide evidence supporting a novel role for MARK2 in promoting malignant phenotypes of lung cancer, and in potentially modulating response to the DNA damaging chemotherapeutic agent cisplatin.

What's new?

Leukemic stem cells (LSC) may be the source of leukemic self-renewal and are often resistant to chemotherapeutic agents. Immunotherapeutic approaches could be the strategy of choice to eliminate such residual malignant cells. To ensure the efficacy of novel immunotherapeutic agents, however, specific target structures on LSC and their immunogenic potential to activate T cells must be identified. This study reveals the expression of several leukemia-associated antigens (LAA) on LSC. Moreover, LAA-specific T cells hamper LSC in immunoassays and in a mouse model. This supports, for the first time in acute myeloid leukemia, the hypothesis that LAA-specific T cells can control leukemic progenitor cells.

What's new?

Patients with triple-negative breast cancer (TNBC) may respond very differently to therapy, despite their apparent similarities. Thus, prognostic and predictive biomarkers are needed in order to identify subgroups that will allow treatment to be individualized. In this study, the authors found that patients with lower expression of a calcium-binding protein called S100A14 had significantly better disease-free survival. In addition to its prognostic value, S100A14 may therefore also be a potential therapeutic target.

What's new?

Gains in stem cell-like properties by tumor cells may be linked to the epithelial-to-mesenchymal transition (EMT), suggesting that changes in the expression of EMT-associated transcription factors are predictive of tumor progression. This study shows that progression of colorectal mucosa from normal to adenomatous to cancerous is accompanied by gradually increasing expression of sine oculis homeobox 1 (SIX1), a transcription factor known to regulate EMT-related mechanisms. In two separate colorectal patient cohorts, elevated SIX1 expression was found to be associated with decreased overall survival. The results indicate that SIX1 is of prognostic value in colorectal cancer.

What's new?

Drinking alcohol and smoking tobacco increase one's risk of cancer. But how much do they influence the risk of developing a subsequent cancer at a different site? In this paper, the authors calculate the risk for patients who had ever been or were currently drinkers or smokers. Not surprisingly, smoking increased the chance of getting a second cancer regardless of alcohol habits; drinking some alcohol increased the risk only when combined with smoking. Heavy drinking and heavy smoking, however, both increased the risk of a later cancer.

What's new?

Prostate cancer is the second most common cancer in men, yet few modifiable risk factors are known. A window to the study of modifiable risk factors is the metabolome, with prospective metabolomic serum profiling being a promising new investigative approach. In prostate cancer, use of this approach had resulted in the identification of numerous circulating lipids associated with risk of aggressive disease. Here, the authors report inverse associations between aggressive disease and energy and lipid metabolites, including alpha-ketoglutarate, citrate, inositol-1-phosphate and several glycerophospholipids and fatty acids. Some of the metabolites may be relevant to prostate cancer development and progression.

What's new?

The recurrence of colon cancer more than 5 years following surgery for curative resection is a significant concern for patients. Yet, little is known about the epidemiology of late recurrence for colon cancer. Here, among more than 3,600 patients who underwent resection with intention to cure, 1 man in every 12 and 1 woman in every 19 was affected by late recurrence, defined as the return of colon cancer between 5 and 10 years after surgery. The findings suggest that regular follow-up beyond 5 years may be needed in order to catch recurrence in a timely manner.

What's new?

At the time of diagnosis, more than one-fifth of colorectal cancer (CRC) patients present with stage IV disease, involving synchronous metastases, which are notoriously difficult to manage. This study suggests that the metastatic pattern in stage IV CRC depends at least in part on the status of the mismatch repair (MMR) system. In particular, deficient MMR was associated with a reduced risk of synchronous metastases confined to the liver. No such association was detected for metastases to the lungs. MMR status also had no impact on survival among stage IV patients.

What's new?

Diet influences endogenous hormone levels such as estradiol but whether these influences affect breast cancer risk remains unclear. The authors examined food pattern associated with estrogens (high in pizza, red meat and legumes; low in coffee and whole grains) in Swedish postmenopausal women and found that a higher estrogen dietary pattern score was associated with increased risk of breast cancer. However, this did not significantly correlate with estrogen receptor status pointing to potentially other cellular processes, i.e., inflammation, that a diet high in red meat and low in coffee is known to affect.

What's new?

Smoking dramatically increases lung cancer risk, yet only about one-fifth of long-term heavy smokers develop the disease. To better understand factors that predict lung cancer in smokers, the authors of the present report analyzed the results of two studies conducted in areas with large Jewish communities, Northern Israel and New York. Data on the more than 10,000 participants in the studies show that lung cancer risk is significantly increased in non-Jews but only moderately elevated in Jews. The differences could not be explained by smoking characteristics (e.g., amount or duration) or by genetic risk variants for lung cancer.

What's new?

Children and adolescents with Hodgkin lymphoma (HL) often have a family history of lymphoid neoplasm (LN), but the role of familial cancer history in pediatric/adolescent HL is not well defined. Here, HL in children and adolescents was found to be associated with an increased number of cancers in first- and second-degree relatives. Associations were most notable for early-onset cancers, cancers in the paternal lineage and LN in first-degree relatives. Tumor Epstein–Barr virus status had no bearing on the associations. The results suggest that children and adolescents with familial clustering of LNs share genetic and environmental risk factors with relatives.

What's new?

Most pancreatic cancer patients do not survive long after diagnosis, and, so far, there are not many genetic markers to help screen for the disease. In search of genetic predictors of pancreatic cancer, the authors zoomed in on a region linked to susceptibility to the disease. They measured the frequency of different variants of two genes, telomerase reverse transcriptase and telomerase RNA component, among thousands of pancreatic cancer patients and controls. They identified several variants of the TERT gene that indicate a boosted pancreatic cancer risk, and which may develop into useful prognostic tools.

What's new?

More than two million workers worldwide are exposed to benzene each year. In this long-term study of Chinese workers, the authors found that chronic benzene exposure was associated with a substantial increase in the risk of myeloid and lymphoid neoplasms, lung cancer, and respiratory diseases. The results also suggest possible associations with other malignant and non-malignant disorders.

What's new?

International comparisons of cancer-screening programs can identify methods for improving screening strategies. In this study, the authors compared breast-cancer screening programs in Denmark and the United States (US). The study found that recall rates in the US were about four times as high as that in Denmark. Although both programs detected a similar percentage of asymptomatic cancers, women in the US were far more likely to have received a false-positive test result, leading to increased patient anxiety and higher costs.

What's new?

Cervical cancer is a leading cause of cancer death among women worldwide, despite the fact that the disease is preventable through screening programs. While routine screening with Pap smear testing has reduced incidence in high-income countries, implementation has largely been unsuccessful in low-resource settings due to insufficient budgets, lack of healthcare delivery infrastructure and competing health priorities. Tailored protocols that maximize health benefits under operational constraints are needed. This study presents a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage and follow-up of screen-positive women, to help decision-makers identify where program investments yield the greatest value.

What's new?

In families with a history of melanoma, carriers of mutations in the CDKN2A gene are often at increased risk of both melanoma and non-melanoma cancers. Whether families lacking CDKN2A mutations, which make up the majority of melanoma families, have similar non-melanoma cancer risks is unclear. Here, members of CDKN2A wild-type melanoma families were found to have no increase in risk of non-skin cancer. The findings suggest that for most CDKN2A wild-type families, cancer predisposition may be attributed to low-risk rather than high-risk genes like CDKN2A. The novel insight has implications for counseling and surveillance of melanoma families.

What's New?

It's no surprise that white Australians get more skin cancer than their cousins in England, because the sun is far stronger in Australia. This study examined melanoma rates among young people in Australia and England. Among children under 10, incidence was low in both countries. Beyond age 10, though, Australians develop the disease in greater numbers. However, over the past decade, melanoma rates among Australians have been steadily decreasing, 6% per year for girls and 12% per year for boys, suggesting that efforts to reduce UV exposure have been effective. Meanwhile, incidence continued to rise each year in England.

What's new?

Pharmacological inhibition of phosphatidylinositide-3-kinase (PI3K)-mediated signaling holds great promise for treating chronic lymphocytic leukemia (CLL). Here, the authors assessed the PI3K-delta-selective inhibitor idelalisib alongside two novel PI3K-delta inhibitors, which additionally target the PI3K-alpha (copanlisib) or gamma (duvelisib) isoforms. They found copanlisib to inhibit the survival of CLL cells at least ten-fold more efficiently than idelalisib and duvelisib. Survival inhibition by copanlisib was cell-type selective, accompanied by strong reduction of chemotaxis, and efficacious in the presence of stroma cell support. Survival inhibition by copanlisib was also enhanced by monoclonal antibodies, while antibody-dependent cell-mediated cytotoxicity for a CLL cell line remained undisturbed.

What's new?

Insulin-like growth factors (IGF) 1 and 2 promote the biogenesis of neuroblastoma, a frequent neuroendocrine tumor in early childhood. Here the authors show that targeting IGF-1 and 2 with a specific antibody (m708.5) has anti-tumor activity in neuroblastoma cell lines as well as in cell culture models of the Ewing family of tumors, rhabdomyosarcoma, and osteosarcoma. Similarly, in xenograft mouse models of neuroblastoma, m798.5 together with an inhibitor of mammalian target of rapamycin (mTOR) suppressed tumor growth and increased survival, supporting a potential clinical application of antibodies targeting IGF-1/2 in children afflicted with solid tumors.

What's new?

The soluble VEGF decoy receptor, FP3 is a highly promising candidate to inhibit tumor angiogenesis. However, it has limited therapeutic efficacy in cancer patients and may elicit toxic side effects. To address this challenge, here the authors designed a novel cancer cell-specific oncolytic adenovirus (Ad) expressing FP3. They report for the first time that the FP3-harboring oncolytic Ad mediates an efficient and long-term antiangiogenic effect and strong antitumor effect in cancer-bearing hosts. The mechanisms of action combine sustained VEGF silencing efficacy and enhanced cancer cell-specific killing. The newly designed system thus provides a novel promising therapeutic approach in the treatment of cancer.

What's new?

Polyethylene glycol (PEG) reduces colon cancer in rats treated with carcinogens. In this study, the authors found that PEG inhibits colon carcinogenesis in Pirc rats (for “polyposis in the rat colon”). Pirc rats carry a mutation in the Apc gene that mimics human familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC) more closely than other Apc-mutated strains. Given the similarities between Pirc rats and human pathology, these results suggest that PEG trials in humans at risk for CRC may be worthwhile.