The role of REV1 in cancer resistance to radiation therapy
Conference Year
January 2021
Abstract
Despite the availability of several treatment modalities, cancer resistance is a prominent clinical challenge. Cancer recurrence is often observed in patients after initial treatment leading to acquired resistance. Amongst the different biological pathways responsible for treatment resistance, translesion synthesis (TLS), a DNA damage tolerance mechanism has recently been implicated in causing cancer resistance to chemotherapy (Yamanaka et al., 2017). The REV1 TLS protein plays a major role in this pathway, where it functions as a key scaffolding protein that helps facilitate DNA damage bypass. Recently, targeting REV1 with small molecule inhibitors was shown to sensitize cancer cells to chemotherapeutic drugs (Wojtaszek et al., 2019). However, it is not known whether REV1 inhibition would similarly sensitize cancer cells to radiation therapy, another common treatment module in cancer patients. We proposed that REV1 is a potential target for sensitizing cancer cells to radiation treatment. We performed cytotoxicity and colony survival assays upon treating cancer cells with REV1 inhibitors and ionizing radiations to determine whether REV1 inhibition similarly sensitizes cancer cells to ionizing radiation (IR) treatment. Remarkably, we found that REV1 inhibition fails to sensitize cells to radiotherapy. Instead, REV1 inhibition induces autophagy which might be enhancing radioresistance. Immunofluorescence assays were used in the detection of autophagy. Ascertaining the mechanisms of REV1-inhibition dependent cancer resistance is a key component in addressing the clinical challenge of cancer therapy resistance.
Primary Faculty Mentor Name
Dr. Nimrat Chatterjee
Graduate Student Mentors
Kanayo Ikeh
Faculty/Staff Collaborators
Kanayo Ikeh (Graduate Student Mentor), Jamie Deutsch (Laboratory Technician), Kira Fisher (Undergraduate Student)
Status
Undergraduate
Student College
College of Agriculture and Life Sciences
Second Student College
Larner College of Medicine
Program/Major
Molecular Genetics
Second Program/Major
Microbiology and Molecular Genetics
Primary Research Category
Biological Sciences
The role of REV1 in cancer resistance to radiation therapy
Despite the availability of several treatment modalities, cancer resistance is a prominent clinical challenge. Cancer recurrence is often observed in patients after initial treatment leading to acquired resistance. Amongst the different biological pathways responsible for treatment resistance, translesion synthesis (TLS), a DNA damage tolerance mechanism has recently been implicated in causing cancer resistance to chemotherapy (Yamanaka et al., 2017). The REV1 TLS protein plays a major role in this pathway, where it functions as a key scaffolding protein that helps facilitate DNA damage bypass. Recently, targeting REV1 with small molecule inhibitors was shown to sensitize cancer cells to chemotherapeutic drugs (Wojtaszek et al., 2019). However, it is not known whether REV1 inhibition would similarly sensitize cancer cells to radiation therapy, another common treatment module in cancer patients. We proposed that REV1 is a potential target for sensitizing cancer cells to radiation treatment. We performed cytotoxicity and colony survival assays upon treating cancer cells with REV1 inhibitors and ionizing radiations to determine whether REV1 inhibition similarly sensitizes cancer cells to ionizing radiation (IR) treatment. Remarkably, we found that REV1 inhibition fails to sensitize cells to radiotherapy. Instead, REV1 inhibition induces autophagy which might be enhancing radioresistance. Immunofluorescence assays were used in the detection of autophagy. Ascertaining the mechanisms of REV1-inhibition dependent cancer resistance is a key component in addressing the clinical challenge of cancer therapy resistance.