Dr. Simone’s laboratory has contributed significantly to understanding mechanisms that underlie cytotoxic treatment resistance and tumor progression by studying the microRNA drivers and effects of cells metabolism via dietary alterations. Her laboratory demonstrated for the first time that caloric restriction (CR) modifies change in vivo at the microRNA level (Orum et al, Cell Cycle. 2012). The Simone laboratory then explored the physiologic impact of CR and demonstrated for the first time that CR can augment radiation therapy (Saleh et al., Cell Cycle. 2013), which she then translated directly into a clinical trial using diet during radiation for early stage breast cancer patients (NCT01819233). The lab found the same improved physiologic response of the primary tumor in vivo when CR was combined with chemotherapy and this was also translated directly to a clinical trial (NCT02827370). The Simone laboratory was also the first to investigate the mechanistic role of microRNAs in the ability of CR to decrease metastatic disease burden via control of the ECM (Jin et al, Breast Cancer Res Treat. 2014 and Simone BA, Cell Cycle. 2016) which is being discussed as a NRG clinical trial concept. To further understand how diet can improve microRNA drivers of cancer progression, her microRNAs role of microRNAs in third IIT is accruing patients with endometrial, prostate and breast cancer who undergo CR before definitive oncologic surgery (NCT02983279).
The overarching focus of the Simone laboratory is to increase the effectiveness of cytotoxic therapy such as radiation and chemotherapy in tumors that have a poor response to standard therapies. To accomplish this, the lab uses diet modification to alter a cells metabolism via signaling pathways to make the cancer cells more vulnerable to cytotoxic therapy. Our studies have found new methods for treating radiation and chemotherapy resistant tumors, which has led to the development of innovative clinical trials.
Our current laboratory projects include using mouse models of hormonally responsive cancers (breast and prostate) to study the nutrient sensitive and inflammatory pathways linked to metabolism. Furthermore, we are looking to understand the alterations in miRNA regulation induced by caloric restriction that can affect the response to radiation and to chemotherapy.
Presently, we are running multiple concurrent trials in the clinical setting focused around Caloric Restriction for Oncology Research (CAREFOR). The original CAREFOR clinical trial looked into how a 25% caloric restriction (CR) for a six week radiation treatment (RT) sandwiched between two weeks of only diet before and after the RT. Our trial patients were able to sustain an 80% compliance to their reduced diet throughout all 10 weeks as evidenced by their weight loss, improved quality of life measures and positive alterations in several serum markers. Molecularly, we were able to see how a caloric restriction during RT can reduce the increase of inflammation through miR-21 serum markers.
This initial CAREFOR trial has paved they way for two concurrent oncology clinical trials here at Jefferson; one focusing on neo-adjuvant patients and the second for patients going directly into surgery. The neo-adjuvant trial was designed to understand how a CR can cause a down-regulation of the dominate molecular drivers of an individuals’ breast cancer and how it will enhance the effect of neo-adjuvant chemotherapy to allow for an increase in the pathologic complete response rate. The pre-operative trial seeks to investigate how caloric restriction may affect microRNA-21 change in the serum of patients with biopsy proven cancer before and after dietary intervention.
The Simone lab is also interested in new technological advances that may play a role in how medicine is utilized and practiced in the near future. We are looking to expand the use of telehealth platforms for patients finishing up radiation treatment to minimize the need for patients to return to the hospital for follow up visits without compromising patient satisfaction or effectiveness of care. Furthermore, we are looking to design a wearable to track and understand desquamation of skin after radiation treatment.