Hot off the presses! Jul 01 Nat Rev Cancer

The Jul 01 issue of the Nat Rev Cancer is now up on Pubget (About Nat Rev Cancer): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

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  - Nat Rev Cancer 11(7):459 (2011)
  
• Leukaemia: Targeted therapy re-enABLed? | PDF (279 KB)
  - Nat Rev Cancer 11(7):460 (2011)
  Targeted therapies that are toxic only to cells with specific oncogenic lesions can be highly effective until resistance mechanisms emerge. A new study identifies BCL-6 overexpression as a resistance mechanism that arises during the targeted treatment of breakpoint cluster region (BCR)–ABL1-positive leukaemias and suggests a potential therapeutic opportunity to overcome this resistance.
• Cancer metabolism: Feed it forward | PDF (226 KB)
  - Nat Rev Cancer 11(7):461 (2011)
  Pyruvate kinase (PK) catalyses a crucial step in glycolysis. The PK isoform PKM2, but not the PKM1 isoform, promotes this pathway in cancer cells, thus facilitating the switch from oxidative phosphorylation to glucose metabolism to generate ATP.
• Imaging: Probing the pancreas | PDF (236 KB)
  - Nat Rev Cancer 11(7):461 (2011)
  Patients with pancreatic ductal adenocarcinoma (PDAC) have a 5-year survival rate of less than 5%, often because patients are not diagnosed until they have late-stage disease. Indeed, evidence suggests that the detection of earlier stages — pancreatic intraepithelial neoplasia (PanIN) — is likely to increase the number of patients diagnosed with surgically resectable tumours and therefore increase survival rates.
• Signalling: Location, location, location | PDF (411 KB)
  - Nat Rev Cancer 11(7):462 (2011)
  Many receptor tyrosine kinases (RTKs) undergo endocytosis, which can alter activation of downstream signalling pathways and promote RTK degradation. For example, endocytosis of epidermal growth factor receptor (EGFR) leads to lysosomal degradation of this RTK, a process that is evaded by some tumours.
• Metastasis: New recruits | PDF (312 KB)
  - Nat Rev Cancer 11(7):462 (2011)
  Macrophages in the tumour microenvironment have diverse roles in tumour progression. Pollard and colleagues previously identified a distinct macrophage subpopulation that is involved specifically in promoting metastasis; they have now examined the origin and function of these metastasis-associated macrophages (MAMs).
• Still hidden behind a screen | PDF (59 KB)
  - Nat Rev Cancer 11(7):462 (2011)
  Patients with ovarian cancer are typically diagnosed with advanced disease, when therapeutic opportunities are limited. So, it is important to be able to detect early stages of ovarian cancer using tools such as biomarkers or imaging.
• Melanoma targets | PDF (97 KB)
  - Nat Rev Cancer 11(7):463 (2011)
  There are few therapeutic options for treating metastatic melanoma, and the prognosis for patients with this disease is poor. However, three recent clinical trials of agents targeting different pathways have reported encouraging results.
• Kidney cancer: An enigma remains | PDF (164 KB)
  - Nat Rev Cancer 11(7):464 (2011)
  The tumour suppressor WTX (also known as FAM123B) is an enigmatic protein in that it is a member of a select group of proteins (designated FAM123) that have no domains with significant homology to proteins of known function. Up to 30% of patients with the kidney cancer Wilms' tumour have somatic mutations in WTX, and, as this gene resides on the X chromosome, mutation of one copy is enough to eliminate gene function.
• Therapeutic resistance: Up or down? | PDF (177 KB)
  - Nat Rev Cancer 11(7):464 (2011)
  Two papers identify new modulators of oestrogen receptor-α (ERα) expression that have implications for the response of ERα+ breast cancer to endocrine therapy.
• Immunology | Signalling | Signalling | Metabiolism | PDF (74 KB)
  - Nat Rev Cancer 11(7):465 (2011)
  Myeloid-derived suppressor cells are implicated in regulating permisiveness for tumor metastasis during mouse gestation Mauti, L. A.et al. J. Clin. Invest.6 Jun 2011 (doi:10.1172/JCI41936)
• Tumour suppression: Shedding light on degradation | PDF (217 KB)
  - Nat Rev Cancer 11(7):466 (2011)
  Constitutive photomorphogenesis protein 1 (COP1) can function as an E3 ubiquitin ligase and has been associated with the degradation of the oncoprotein JUN and the tumour suppressor p53. Using different approaches, two recent papers have shown that COP1 can suppress tumorigenesis.
• DNA interstrand crosslink repair and cancer
  - Nat Rev Cancer 11(7):467 (2011)
  Interstrand crosslinks (ICLs) are highly toxic DNA lesions that prevent transcription and replication by inhibiting DNA strand separation. Agents that induce ICLs were one of the earliest, and are still the most widely used, forms of chemotherapeutic drug. Only recently, however, have we begun to understand how cells repair these lesions. Important insights have come from studies of individuals with Fanconi anaemia (FA), a rare genetic disorder that leads to ICL sensitivity. Understanding how the FA pathway links nucleases, helicases and other DNA-processing enzymes should lead to more targeted uses of ICL-inducing agents in cancer treatment and could provide novel insights into drug resistance.
• SWI/SNF nucleosome remodellers and cancer
  - Nat Rev Cancer 11(7):481 (2011)
  SWI/SNF chromatin remodelling complexes use the energy of ATP hydrolysis to remodel nucleosomes and to modulate transcription. Growing evidence indicates that these complexes have a widespread role in tumour suppression, as inactivating mutations in several SWI/SNF subunits have recently been identified at a high frequency in a variety of cancers. However, the mechanisms by which mutations in these complexes drive tumorigenesis are unclear. In this Review we discuss the contributions of SWI/SNF mutations to cancer formation, examine their normal functions and discuss opportunities for novel therapeutic interventions for SWI/SNF-mutant cancers.
• The Hedgehog's tale: developing strategies for targeting cancer
  - Nat Rev Cancer 11(7):493 (2011)
  Research into basic developmental biology has frequently yielded insights into cancer biology. This is particularly true for the Hedgehog (HH) pathway. Activating mutations in the HH pathway cause a subset of sporadic and familial, skin (basal cell carcinoma) and brain (medulloblastoma) tumours. Furthermore, the growth of many human tumours is supported by HH pathway activity in stromal cells. Naturally occurring and synthetic inhibitors of HH signalling show great promise in animal models and in early clinical studies. However, it remains unclear how many cancers will ultimately benefit from these new, molecularly targeted therapies.
• Pro-senescence therapy for cancer treatment
  - Nat Rev Cancer 11(7):503 (2011)
  Abundant evidence points to a crucial physiological role for cellular senescence in combating tumorigenesis. Thus, the engagement of senescence may represent a key component for therapeutic intervention in the eradication of cancer. In this Opinion article, we focus on concepts that are relevant to a pro-senescence approach to therapy and we propose potential therapeutic strategies that aim to enhance the pro-senescence response in tumours.
• The physics of cancer: the role of physical interactions and mechanical forces in metastasis
  - Nat Rev Cancer 11(7):512 (2011)
  Metastasis is a complex, multistep process responsible for >90% of cancer-related deaths. In addition to genetic and external environmental factors, the physical interactions of cancer cells with their microenvironment, as well as their modulation by mechanical forces, are key determinants of the metastatic process. We reconstruct the metastatic process and describe the importance of key physical and mechanical processes at each step of the cascade. The emerging insight into these physical interactions may help to solve some long-standing questions in disease progression and may lead to new approaches to developing cancer diagnostics and therapies.
• Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells
  - Nat Rev Cancer 11(7):523 (2011)
  Cancers of the breast and other tissues arise from aberrant decision-making by cells regarding their survival or death, proliferation or quiescence, damage repair or bypass. These decisions are made by molecular signalling networks that process information from outside and from within the breast cancer cell and initiate responses that determine the cell's survival and reproduction. Because the molecular logic of these circuits is difficult to comprehend by intuitive reasoning alone, we present some preliminary mathematical models of the basic decision circuits in breast cancer cells that may aid our understanding of their susceptibility or resistance to endocrine therapy.
• Correspondence: Is vasculogenesis crucial for the regrowth of irradiated tumours?
  - Nat Rev Cancer 11(7):532 (2011)
  We have read with interest the Review by Begg, Stewart and Vens (Strategies to improve radiotherapy with targeted drugs. Nature Rev. Cancer 11, 239–253 (2011)