Roberto Vargas, MD
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Endometrial carcinoma is the sixth most common malignancy in women worldwide. However, it represents one of the few malignancies for which mortality is increasing, highlighting the immediate need for improved diagnosis and treatment strategies for this disease. In general, diagnosis and treatment is based upon separation into two primary histologic subtypes, low-grade endometrioid and high-grade serous. The majority of women present with early-stage, low-grade endometrioid cancer and have favorable outcomes after radiation treatment. High-grade serous tumors are more aggressive and tend to respond poorly to chemotherapy and radiation. However, there are a small number of low-grade endometrioid tumors that can recur after radiation therapy and become aggressive, resulting in poor outcomes. Thus, a treatment strategy based solely on grade, stage, and histologic subtype is not ideal. The overarching goal of the Vargas Lab is to identify the genomic alterations in these tumors that result in resistance to radiation therapy and recurrence.
To this end, our current work focuses on the consequences of mutations in the TP53 cell cycle regulatory gene on radiation resistance in endometrial carcinoma. This work is based on a recent genomic profiling study published by The Cancer Genome Atlas (TCGA) (Kandoth et al., Nature 2018), which classified endometrial carcinomas into distinct genomic subtypes. The most aggressive subtype displayed a high number of both somatic copy-number alterations (SCNAs) and mutations in the TP53 gene. 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, allowing continued proliferation of copy number-altered tumor cells and recurrence. Our lab is systematically testing the role of these individual p53 mutations on 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 overexpression of p53 mutant cDNAs in a p53-null background, along with high-content radiation profiling. Our goal is to eventually use these tools to assess the role of other altered genes in radiation resistance.
Dr. Roberto Vargas is a clinican scientist working to build a lab focused on gynecologic cancers. Current projects explore which genetic factors may make endometrial carcinoma resistant to radiation therapy.
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.
Findings from a new retrospective study reveal that caution should be practiced when prescribing antibiotics to patients as antibiotic therapy is associated with decreased overall survival among women with the ovarian cancer.