Roberto Vargas Laboratory

Research

Endometrial carcinoma is the most common gynecologic malignancy. It also represents one of two malignancies for mortality rates have not improved over the last 30 years, highlighting the immediate need for innovative research and treatment strategies. The majority of women present with early-stage, low-grade endometrioid cancer and have favorable outcomes after surgery. A smaller portion present with high-grade, TP53-mutated tumors, commonly labeled as “serous-type”. These types of endometrial cancers are associated with higher risk of advanced stage at diagnosis, higher risk of recurrence, poor response to immunotherapy, and significant racial disparities in terms of incidence and outcomes. The overarching goal of the Vargas Lab is to identify the genomic alterations in these tumors that contribute to resistance and exploit these findings to improve response to radiotherapy and chemotherapy. To this end, our current work focuses on 1) the consequences of mutations in the TP53 cell cycle regulatory gene on radiation resistance in endometrial carcinoma and 2) evolutionary adaptations to therapy that are afforded by these genetic events.

In response to DNA-damaging radiation therapy, we hypothesize that most of these TP53 mutations in this subtype result in loss of its checkpoint functions, directly contributing to their radiation-resistant phenotypes. Our lab is systematically testing the role of these individual TP53 mutations on p53 signaling and radiation resistance in endometrial cancer cell lines by utilizing a combination of cell and molecular biology tools. This includes an intron/exon junction CRISPR-Cas9 knockout strategy, which facilitates the overexpression of p53 mutant cDNAs in a p53-null background, along with high-content radiation profiling. Furthermore, we aim to pharmacologically target and exploit these pathways in an attempt to improve response to current therapies.

Therapeutic resistance is a result of evolutionary adaptation. Taking that into consideration, we also utilize evolutionary experimentation to help identify common resistance pathways that these high-risk endometrial cancers exploit to escape therapy. The ability to identify these evolving resistant states in real-time would ultimately allow for pro-active treatment changes, as well as personalizing subsequent treatments to predicted novel sensitivity states based on said adaptations

Selected Publications

View publications for Roberto Vargas, MD
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Vargas R, Gopal P, Kuzmishin GB, DeBernardo R, Koyfman SA, Jha BK, Mian OY, Scott J, Adams DJ, Peacock CD, Abazeed ME. Case study: patient-derived clear cell adenocarcinoma xenograft model longitudinally predicts treatment response. NPJ Precis Oncol.  (2018) 2(14):  doi: 10.1038/s41698-018-0060-3.  PMID: 30202792

Moulton L, Vargas R, Michener C. (2019). Sentinel lymph node mapping in endometrial and cervical cancer: a survey of practices and attitudes in gynecologic oncologists. Journal of Gynecologic Oncology. 30. 10.3802/jgo.2019.30.e35.

Connor E.V., Newlin E.M., Vargas R, AlHilli M.M.. (2018). Non-home discharge is associated with longer interval to adjuvant chemotherapy and increased 90-day mortality in women undergoing surgery for epithelial ovarian cancer. Gynecologic Oncology. 149. 624. 10.1016/j.ygyno.2018.03.021.

Vargas R, Vargas C.R., Costales A, Connor E.V., Ricci S.. (2018). Readability of online hysterectomy literature: Too difficult for our patients to read?. Gynecologic Oncology. 149. 630-631. 10.1016/j.ygyno.2018.03.036.

Mahdi H, Han X, Moulton L, Vargas R. Trends in Survival of Patients with Uterine Serous Carcinoma from 1988 to 2011: A Population-Based Study. International Journal of Gynecologic Cancer 2017;27:1155-1164.

Mahdi H, Xiaozhen H., Rose P.G., Vargas R. (2016). Disparity in survival between white and African American patients with uterine serous carcinoma: Changes in clinical characteristics, pattern of care and outcome over time from 1988 to 2011. Gynecologic Oncology. 141. 61-62. 10.1016/j.ygyno.2016.04.181.

Rauh-Hain J, Foley O.W., Clark R, Vargas R, Hinchcliff E, Esselen K, Horowitz N, Carmen M.. (2015). Clinical characteristics and outcomes of patients with stage I epithelial ovarian cancer compared to fallopian tube cancer. Gynecologic Oncology. 137. 110. 10.1016/j.ygyno.2015.01.272.

Vargas R, Rauh-Hain J, Iafrate, Chung D, Ellisen L, Shannon K, Rodgers L, Oliva E, Schorge J. (2015). Lynch syndrome screening in endometrial cancer patients with immunohistochemistry: A single center experience. Gynecologic Oncology. 136. 407. 10.1016/j.ygyno.2014.11.058.

Vargas R, Rauh-Hain J, Esselen K, Horowitz N, Schorge J.O., Carmen M.G., Growdon W. (2014). Distribution of ovarian cancer recurrence following intravenous (IV) and intraperitoneal (IP) adjuvant chemotherapy after upfront cytoreductive surgery. Gynecologic Oncology. 133. 70-71. 10.1016/j.ygyno.2014.03.190.

Vargas R, Rauh-Hain J, Clemmer J, Clark R, Goodman A, Growdon W, Schorge J, Carmen M, Horowitz N, Boruta II D. (2014). Tumor size, depth of invasion, and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: A SEER analysis. Gynecologic Oncology. 133. 10.1016/j.ygyno.2014.02.011.

Rauh-Hain J, Vargas R, Clemmer J, Clark R, Bradford L, Growdon W, Goodman A, Boruta II D, Schorge J, Carmen M. (2014). Mucinous Adenocarcinoma of the Endometrium Compared With Endometrioid Endometrial Cancer: A SEER Analysis. American journal of clinical oncology. 39. 10.1097/COC.0000000000000015.

Diver E, May T, Vargas R, Bernstein M, Goldstein D, Berkowitz R. (2013). Changes in Clinical Presentation of Postterm Choriocarcinoma at the New England Trophoblastic Disease Center in Recent Years.. Gynecologic Oncology. 130. 10.1016/j.ygyno.2013.06.014.