AACR Journals to Share Editors’ Picks

The American Association for Cancer Research (AACR) publishes eight esteemed scientific journals. Each month, these journals feature a wide range of peer-reviewed research that encompasses the entire spectrum of cancer science. Some of the world’s leading cancer scientists publish articles in our journals, contributing greatly toward the AACR’s mission to prevent and cure cancer through research, education, communication, and collaboration.

We are pleased to debut a new feature on the blog, Editors’ Picks. Each month, AACR journal editors will share a curated list of original articles, representing each publication. While our journals are subscription-based, the stories featured in Editors’ Picks will be freely available for the month.

The staff at Cancer Research Catalyst is excited about sharing the wealth of knowledge that’s available in our journals. Check back each month for the latest Editors’ Picks.

Journal: Cancer Epidemiology, Biomarkers & Prevention

Differences in Breast Cancer Survival by Molecular Subtypes in the United States

Using data from the Surveillance, Epidemiology, and End Results (SEER) registry, the authors analyzed four-year breast cancer survival rates based on molecular subtypes as defined by hormone receptor (HR) and HER2 status. The best survival rate was observed among women with HR+/HER2- breast cancer and the worst survival rate was observed among women with triple-negative breast cancer. Importantly, cancer stage at diagnosis substantially affected survival, and contrary to conventional thought, women with HR+/HER2+ breast cancer displayed better survival rates than women with HR+/HER2- breast cancer in advanced-stage disease, likely attributable to major advances in HER2-targeted treatment.

Journal: Molecular Cancer Research

PI3K Positively Regulates YAP and TAZ in Mammary Tumorigenesis Through Multiple Signaling Pathways

The study found that YAP and TAZ, two transcriptional regulators, are critical mediators of HER2- and PI3K-induced tumorigenesis. PIK3CA and PIK3CB are subunits of PI3K that are frequently altered in breast cancers. The authors describe that PIK3CA and PIK3CB positively regulate YAP and TAZ in mammary tumorigenesis. The findings suggest the potential role of YAP and TAZ as biomarkers of breast carcinogenesis, and provide a new rationale for targeting them, alone or in combination with PI3K inhibitors, for breast cancer treatment.

Journal: Cancer Research (June 1 issue)

Therapeutic Targeting of Sunitinib-induced AR Phosphorylation in Renal Cell Carcinoma

Treatment for renal cell carcinoma (RCC) includes the use of sunitinib, a receptor tyrosine kinase inhibitor, but many patients develop resistance to this therapy. Here, the authors found that androgen receptor (AR) expression was increased in sunitinib-resistant RCC cell lines and patient-derived xenografts. Treatment with the AR antagonist enzalutamide induced both the degradation of the AR and attenuated its downstream activity in sunitinib-resistant RCC cells, and dual treatment with sunitinib and enzalutamide in an in vivo RCC model with acquired sunitinib resistance efficiently induced tumor regression. These findings suggest that targeting the AR may be a viable therapeutic strategy to overcome RCC resistance to receptor tyrosine kinase inhibitors.

Journal: Clinical Cancer Research (June 1 issue)

Optical Analysis of Glioma: Fourier-Transform Infrared Spectroscopy Reveals the IDH1 Mutation Status

IDH1 is an enzyme involved in glucose metabolism, and mutations in IDH1 can drive gliomas. Because patients with IDH1 wild-type gliomas experience decreased survival compared with patients that harbor IDH1-mutated tumors of the same histologic grade, determining IDH1 mutation status could impact prediction and prognosis of the disease. This study describes how vibrational spectroscopy can provide intraoperative diagnostic information on the IDH1 mutation status of human glioma samples in seconds. Using this technology in real-time during surgery might allow the rapid online diagnosis of the IDH1 genotype, and could facilitate the decision to conduct definitive neurosurgical resection and may guide future therapeutic strategies.

Journal: Molecular Cancer Therapeutics

ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment

Cyclin-dependent kinase 7 regulates key events during cell cycle progression and several transcription factors, including ERα. This is the first report that describes the utility of ICEC0942, an orally bioavailable selective CDK7 inhibitor, as a single agent or in combination with hormone therapies for the treatment of estrogen receptor α (ERα)-positive breast cancer. Deregulation of CDKs is a common feature in several cancers, which suggests that in addition to ERα-positive breast cancer, ICEC0942 may have therapeutic impact in treating several other cancers, including acute leukemia and small-cell lung cancer.

Journal: Cancer Research (June 15 issue)

Zika virus selectively kills aggressive human embryonal CNS tumor cells in vitro and in vivo

Zika virus (ZIKV), which made headlines in South and Central Americas a few years ago when it was discovered that the virus can cause microcephaly and other abnormalities in infants, could potentially be useful in treating cancers. A specific strain, the Brazilian Zika virus strain (ZIKVBR), showed antitumor properties in human breast, prostate, colorectal, and embryonal central nervous system (CNS) tumor cell lines, and in mice bearing human embryonal CNS tumor xenografts. The study provides new insights into its anticancer mechanisms and suggests further investigations in using ZIKVBR or engineered derivatives to develop oncolytic therapies against highly aggressive and metastatic CNS tumors.

Journal: Cancer Discovery

Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers

The study provides proof of principle for targeting ERBB3 (HER3) in NRG1-rearranged cancers. In contrast, targeting ERBB2 (HER2/neu) was not as effective in patients with NRG1-rearranged cancers despite preclinical and clinical data supporting its use. While NRG1 fusions are largely found in invasive mucinous adenocarcinomas of the lung, the authors identified NRG1 rearrangements across various solid tumors, including pancreatic adenocarcinoma and breast carcinoma, through analysis of large genomic datasets. The findings suggest the utility of targeting ERBB3 in NRG1-rearranged cancers and support a basket trial to test this approach.

Journal: Clinical Cancer Research (June 15 issue)

A Phase I Clinical Trial of AZD1775 in Combination with Neoadjuvant Weekly Docetaxel and Cisplatin before Definitive Therapy in Head and Neck Squamous Cell Carcinoma

The tyrosine kinase WEE1 is a cell cycle checkpoint regulator that maintains genomic stability and is essential for DNA repair and survival in head and neck squamous cell carcinoma (HNSCC) with mutations in the tumor suppressor gene p53. This study reported on data from a phase I trial evaluating the combination of AZD1775, a WEE1 inhibitor, and the chemotherapies cisplatin and docetaxel in patients with late-stage HNSCC who were candidates for definitive chemoradiation. Treatment responses were seen in about half of evaluable patients. Due to its favorable safety profile, the authors infer that AZD1775 could reduce morbidity compared to alternative therapies in borderline-resectable, advanced HNSCC.

Journal: Cancer Prevention Research

The Combined Association of Modifiable Risk Factors with Breast Cancer Risk in the Women’s Health Initiative

The authors used a healthy lifestyle index (HLI) score to assess the association of a combination of modifiable risk factors (diet, alcohol, physical activity, BMI, and smoking) with the risk of invasive breast cancer in postmenopausal women using data from the Women’s Health Initiative (WHI). According to this analysis, for every unit increase in HLI score, the risk of breast cancer was reduced by 4 percent. Furthermore, compared with women with an HLI score in the lowest quintile, those with a score in the highest quintile had a 30 percent lower risk for any breast cancer. These findings suggest that promoting a healthy lifestyle may help lower breast cancer risk among postmenopausal women.

Journal: Cancer Immunology Research

IL17A Regulates Tumor Latency and Metastasis in Lung Adeno and Squamous SQ.2b and AD.1 Cancer

This study found that tumor-infiltrating lymphocytes (TILs) analyzed from patients with early-stage non-small cell lung cancer (NSCLC) had increased expression of the cytokine IL17A as compared with adjacent tumor-free tissue. In contrast, patients with late-stage NSCLC had decreased Th17 cells (a type of T cell that facilitates the production of IL-17) in their tumor-positive lymph nodes compared to tumor-free lymph nodes, indicating that the immune response in NSCLC may be regulated by Th17 cells. The deletion of IL17A promoted metastasis in a mouse model of NSCLC, and adoptive transfer of IL17a-sufficient CD4+ T cells reduced tumor incidence and metastasis in this model. Taken together, these findings support an important function of Th17 cells in TILs of NSCLC and suggest both biomarker and therapeutic strategies for human lung cancer.