Mehta receives major grant from American Cancer Society for ovarian cancer research

The Mehta lab is part of 'very select group' to earn an award from the American Cancer Society.
Mehta receives major grant from American Cancer Society for ovarian cancer research

Assistant Professor Geeta Mehta has been awarded a Research Scholar Grant from the American Cancer Society for her research project, “Ovarian Cancer Tumoroids to Study Heterogeneity and Chemoresistance.”

“We look for the brightest minds to answer the toughest questions,” the American Cancer Society stated in its award letter to Mehta. “You are part of a very select group of scientists and healthcare professionals who have received grants from the American Cancer Society over the last 70 years. Thank you for your continued, dedicated efforts to attack cancer from every angle, advancing our mission to save lives, celebrate lives, and lead the fight for a world without cancer.”

Cells that comprise cancerous tumors are highly heterogeneous. Recent research has indicated that this heterogeneity is one of the reasons for buildup of chemotherapy resistance and failure of treatments. Through her meticulous research, Mehta has devised a modular platform that can recreate the heterogeneity of patients’ tumors, using a small number of patient-derived cells. Her lab grows these cultured cell masses, called tumoroids, in a specialized growth medium in tiny droplets. Arrays of these droplets containing patient derived tumoroids can then be utilized for precision oncology and for probing reciprocal relationships between the diverse cell types, that confer chemoresistance. Her lab’s developed methods yield 3D tumor microtissues that bear resemblance to the patients’ own tumors, and  thus serve as important replicas of the cancers in the body.

In the awarded project, Mehta lab is focused on ovarian cancers, which are most lethal gynecologic cancers, causing 150,000 deaths yearly worldwide. Most women who face ovarian cancers develop fluid filled abdomen, called ascites. These malignant ascites contain chemoresistant cells, and cancer stem cells, which can sprout new tumor cells, grow new tumors in distant sites, and are therapy resistant. Moreover, due to the routine bodily movements, the fluid filled abdominal cavity exposes cancer cells to fluid shear stress. The role of shear stress and cell-cell interactions in maintaining and enriching therapy resistant cells and cancer stem cells are not known within the ovarian ascites. As part of the ACS grant, Mehta and her team will uncover these relationships with the 3D patient centered models created in her lab. Her eventual goal is to use these patient derived tumoroids as a testing ground where doctors could quickly try out many different medications, finding the best combination for an individual patient and adjusting on the fly as the disease evolves. This could help them stay one step ahead of the tumor cells inside the patient’s body. The Mehta lab is collaborating with ovarian cancer scientists and clinicians Dr. Karen McLean and Dr. Ronald Buckanovich, as well as computational medicine and bioinformatics expert Dr. Arvind Rao, to successfully complete this project.

“Today we’re limited to two-dimensional cells grown in bovine serum that’s derived from cows. Cells grown this way often don’t respond to medication the same way as ovarian cancer cells inside the body,” said Mehta. “Three-dimensional cultured tumoroids  created from patients’ own cells provide a much more predictive way to test many different medications, and identify combination of drugs that can overcome chemoresistance. Moreover, these lab-built models help us identify key biological questions, including the role of mechanical forces such as shear stress and cell-cell communications in the cancers as they progress and spread.”

While widespread clinical use is likely years off, Mehta says the team now plans to do more extensive testing, culturing cells from patients who are undergoing chemotherapy, then administering the same chemotherapy drugs to the cultured cells and measuring their response. Additionally, their research will provide a modular platform for the study of various critical cell-cell interactions in the malignant ovarian ascites. Their work will also help understand the individual and collective role of heterogenous cell types in enrichment and chemoresistance of cancer stem cells. Their platform will also educate cancer clinicians and researchers about the relevance of considering not only the three-dimensional nature of the cancers, but also the mechanical forces that influence cancer cells.  The results from their research will also be crucial in identifying malignant ascites conditions that can serve as prognostic indicators to predict disease recurrence.

“Even among cancers, ovarian cancer is particularly menacing,” Mehta said. “It is deadly adaptability contributes to a 70-percent relapse rate among patients who have had surgery to remove a tumor. 

“We are overwhelmingly grateful to the American Cancer Society for this grant, which will go a long way in helping us develop a faster, cheaper and more humane way to rapidly test a patient’s response to dozens of therapeutics.”