An expanded universe of cancer targets

Hahn, William C.; Bader, Joel S.; Braun, Theodore P.; Califano, Andrea; Clemons, Paul A.; Druker, Brian J.; Ewald, Andrew J.; Fu, Haian; Jagu, Subhashini; Kemp, Christopher J.; Kim, William; Kuo, Calvin J.; McManus, Michael T.; Mills, Gordon B.; Mo, Xiulei; Sahni, Nidhi; Schreiber, Stuart L.; Talamas, Jessica A.; Tamayo, Pablo; Tyner, Jeffrey W.; Wagner, Bridget K.; Weiss, William A.; Gerhard, Daniela S.; Dančík, Vlado; Gill, Shubhroz; Hua, Bruce K.; Sharifnia, Tanaz; Viswanathan, Vasanthi S.; Zou, Yilong; Cruz, Filemon S. Dela; Kung, Andrew L.; Stockwell, Brent R.; Boehm, Jesse S.; Dempster, Josh; Manguso, Robert T.; Vázquez, Francisca; Cooper, Lee; Du, Yuhong; Ivanov, Andrey A.; Lonial, Sagar; Moreno, Carlos S.; Niu, Qiankun; Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Reyna, Matthew A.; Zhou, Wei; Grandori, Carla; Shmulevich, Ilya; Swisher, Elizabeth M.; Cai, Jitong; Chan, Issac S.; Dunworth, Matthew; Ge, Yuchen; Georgess, Dan; Grasset, Eloïse M.; Henriet, Elodie; Knútsdóttir, Hildur; Lerner, Michael G.; Padmanaban, Veena; Perrone, Matthew; Suhail, Yasir; Tsehay, Yohannes; Warrier, Manisha; Morrow, Quin; Nechiporuk, Tamilla; Long, Nicola; Saultz, Jennifer N.; Kaempf, Andy; Minnier, Jessica; Tognon, Cristina E.; Kurtz, Stephen E.; Agarwal, Anupriya; Brown, Jordana; Watanabe-Smith, Kevin; Vu, Tania Q.; Jacob, Thomas; Yan, Yunqi; Robinson, Bridget A.; Lind, Evan F.; Kosaka, Yoko; Demir, Emek; Estabrook, Joseph; Grzadkowski, Michael; Nikolova, Olga; Chen, Ken; Deneen, Ben; Liang, Han; Bassik, Michael C.; Bhattacharya, Asmita; Brennan, Kevin; Curtis, Christina; Gevaert, Olivier; Ji, Hanlee P.; Karlsson, Kasper; Karagyozova, Kremena; Lo, Yuan–Hung; Liu, Katherine; Nakano, Michitaka; Sathe, Anuja; Smith, Amber Rae; Spees, Kaitlyn; Wong, Wing Hing; Yuki, Kanako; Hangauer, Matt; Kaufman, Dan S.; Balmain, Allan; Bollam, Saumya; Chen, Wei-Ching; Fan, Qi-Wen; Kersten, Kelly; Krummel, Matthew F.; Li, Yun R.; Ménard, Marie; Nasholm, Nicole; Schmidt, Christin; Serwas, Nina K.; Yoda, Hiroyuki; Ashworth, Alan; Bandyopadhyay, Sourav; Bivona, Trevor; Eades, Gabriel; Oberlin, Stefan; Tay, Neil Q.; Wang, Yuhao; Weissman, Jonathan S.

doi:10.1016/j.cell.2021.02.020

Cited by 145 publications

(120 citation statements)

References 131 publications

(137 reference statements)

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“…For the identification of biomarkers of potential diagnostic, prognostic, predictive, or therapeutic interest, comprehensive molecular characterization of cancer, by comparing molecular profiles of cancer and normal tissue from the same anatomical site is essential [ 17 ]. In recent years, several studies have investigated genomic changes, e.g., somatic mutations and copy number variations in VSCC, and its precursor lesion, vulvar intraepithelial neoplasia (VIN) [ 7 , 10 , 11 , 12 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Dasgupta

Ewing‐Graham

Swagemakers

et al. 2021

Cancers

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DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ± 0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.

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Section: Introductionmentioning

confidence: 99%

Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Dasgupta

Ewing‐Graham

Swagemakers

et al. 2021

Cancers

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“…A number of highly active new targeted therapies become available for diseases that are extremely difficult to treat. 13 The pandemic likely jeopardized the development of new drugs as well as the identification and validation of innovative biomarkers for diagnosis anticipation and prognosis prediction. This will negatively impact cancer patients' prognosis in the short term.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 epidemic strongly affected cancer research in Italy: a survey of the Italian Cancer Society (SIC)

et al. 2021

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Background: Italy was among the first countries hit by the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The application of strict lockdown measures disproportionately affected both cancer patient care as well as basic and translational cancer research. Materials and methods: The Italian Cancer Society (SIC) conducted a survey on the effect of lockdown on laboratories involved in cancer research in Italy. The survey was completed by 570 researchers at different stages of their career, working in cancer centers, research institutes and universities from 19 Italian regions. Results: During the lockdown period, the impact of the COVID-19 pandemic emergency on face-to-face research activities was high, with a complete (47.7%) or partial (36.1%) shutdown of the laboratories. In the post-lockdown period, research activities were resumed in most of the respondents' institutions (80.4%), though with some restrictions (77.2%). COVID-19 testing was offered to research personnel only in~50% of research institutions. Overall, the response to the pandemic was fragmented as in many cases institutions adopted different strategies often aimed at limiting possible infections without a clearly defined contingency plan. Nevertheless, research was able to provide the first answers and possible ways out of the pandemic, also with the contribution of many cancer researchers that sacrificed their research programs to help overcome the pandemic by offering their knowledge and technologies. Conclusions: Given the current persistence of an emergency situation in many European countries, a more adequate organization of research centers will be urgent and necessary to ensure the continuity of laboratory activities in a safe environment.

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“…The list of target molecules proposed for cancer therapy is expanding day by day. Therefore, it is quite important to consider how discoveries made in preclinical models are translated to clinical trials designed to test whether modulating the activity of specific targets leads to a clinical response [80]. In particular, with respect to OCCC (which is a rare cancer), application of treatment modalities that are either established or are being tested on other major types of cancer would be a way forward.…”

Section: Future Directionsmentioning

confidence: 99%

Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma

Takahashi

Takenaka

Okamoto

et al. 2021

Cancers

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Ovarian clear cell carcinoma (OCCC) is a histological subtype of ovarian cancer that is more frequent in Asian countries (~25% of ovarian cancers) than in US/European countries (less than 10%). OCCC is refractory to conventional platinum-based chemotherapy, which is effective against high-grade serous carcinoma (HGSC), a major histological subtype of ovarian cancer. Notably, deleterious mutations in SWI/SNF chromatin remodeling genes, such as ARID1A, are common in OCCC but rare in HGSC. Because this complex regulates multiple cellular processes, including transcription and DNA repair, molecularly targeted therapies that exploit the consequences of SWI/SNF deficiency may have clinical efficacy against OCCC. Three such strategies have been proposed to date: prioritizing a gemcitabine-based chemotherapeutic regimen, synthetic lethal therapy targeting vulnerabilities conferred by SWI/SNF deficiency, and immune checkpoint blockade therapy that exploits the high mutational burden of ARID1A-deficient tumor. Thus, ARID1A deficiency has potential as a biomarker for precision medicine of ovarian cancer.

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An expanded universe of cancer targets

Cited by 145 publications

References 131 publications

Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

COVID-19 epidemic strongly affected cancer research in Italy: a survey of the Italian Cancer Society (SIC)

Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma

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