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A bromodomain and extraterminal (BET) inhibitor known as RVX2135 has shown preclinical activity against Myc-driven lymphoma.
Both in vitro and in vivo, RVX2135 inhibited proliferation and prompted apoptosis in lymphoma cells.
Investigation revealed that RVX2135 induces effects similar to those of histone deacetylase (HDAC) inhibitors. Furthermore, RVX2135 and the HDAC inhibitor vorinostat demonstrated synergy in lymphoma-bearing mice.
Jonas Nilsson, PhD, of the University of Gothenburg in Sweden, and his colleagues reported these results in Proceedings of the National Academy of Sciences.
The researchers first evaluated the in vitro antiproliferative effects of RVX2135 and another BET inhibitor called JQ1. They tested the inhibitors on lymphoma cells from Myc-transgenic mice and found that both restricted proliferation and induced apoptosis in a dose-dependent manner.
Next, the team tested RVX2135 in 2 mouse models of lymphoma. The inhibitor was most effective in mice transplanted with dispersed lymphoma from a λ-Myc mouse (ID 2749).
In fact, RVX2135 doubled both the median and overall survival of mice carrying 2749 lymphoma, when compared to vehicle-treated controls.
Dr Nilsson and his colleagues then investigated the mechanism behind these effects. They found that RVX2135 induces a complex transcriptional program without specifically inactivating transgenic Myc transcription.
By examining the genes induced by BET inhibition, the researchers discovered that RVX2135 activates the same genes as those activated by HDAC inhibitors.
So the team tested the HDAC inhibitor vorinostat in combination with RVX2135. And the combination increased survival in mice with 2749 lymphoma, when compared to either inhibitor alone.
“It was also possible to reduce the dose of HDAC inhibitors when used in combination with RVX2135, and this reduced adverse effects,” Dr Nilsson said.
“We see this as a breakthrough in the clinical development of this type of treatment. [W]e believe that the prospects for success with combination treatments are good.” 
A bromodomain and extraterminal (BET) inhibitor known as RVX2135 has shown preclinical activity against Myc-driven lymphoma.
Both in vitro and in vivo, RVX2135 inhibited proliferation and prompted apoptosis in lymphoma cells.
Investigation revealed that RVX2135 induces effects similar to those of histone deacetylase (HDAC) inhibitors. Furthermore, RVX2135 and the HDAC inhibitor vorinostat demonstrated synergy in lymphoma-bearing mice.
Jonas Nilsson, PhD, of the University of Gothenburg in Sweden, and his colleagues reported these results in Proceedings of the National Academy of Sciences.
The researchers first evaluated the in vitro antiproliferative effects of RVX2135 and another BET inhibitor called JQ1. They tested the inhibitors on lymphoma cells from Myc-transgenic mice and found that both restricted proliferation and induced apoptosis in a dose-dependent manner.
Next, the team tested RVX2135 in 2 mouse models of lymphoma. The inhibitor was most effective in mice transplanted with dispersed lymphoma from a λ-Myc mouse (ID 2749).
In fact, RVX2135 doubled both the median and overall survival of mice carrying 2749 lymphoma, when compared to vehicle-treated controls.
Dr Nilsson and his colleagues then investigated the mechanism behind these effects. They found that RVX2135 induces a complex transcriptional program without specifically inactivating transgenic Myc transcription.
By examining the genes induced by BET inhibition, the researchers discovered that RVX2135 activates the same genes as those activated by HDAC inhibitors.
So the team tested the HDAC inhibitor vorinostat in combination with RVX2135. And the combination increased survival in mice with 2749 lymphoma, when compared to either inhibitor alone.
“It was also possible to reduce the dose of HDAC inhibitors when used in combination with RVX2135, and this reduced adverse effects,” Dr Nilsson said.
“We see this as a breakthrough in the clinical development of this type of treatment. [W]e believe that the prospects for success with combination treatments are good.”
A bromodomain and extraterminal (BET) inhibitor known as RVX2135 has shown preclinical activity against Myc-driven lymphoma.
Both in vitro and in vivo, RVX2135 inhibited proliferation and prompted apoptosis in lymphoma cells.
Investigation revealed that RVX2135 induces effects similar to those of histone deacetylase (HDAC) inhibitors. Furthermore, RVX2135 and the HDAC inhibitor vorinostat demonstrated synergy in lymphoma-bearing mice.
Jonas Nilsson, PhD, of the University of Gothenburg in Sweden, and his colleagues reported these results in Proceedings of the National Academy of Sciences.
The researchers first evaluated the in vitro antiproliferative effects of RVX2135 and another BET inhibitor called JQ1. They tested the inhibitors on lymphoma cells from Myc-transgenic mice and found that both restricted proliferation and induced apoptosis in a dose-dependent manner.
Next, the team tested RVX2135 in 2 mouse models of lymphoma. The inhibitor was most effective in mice transplanted with dispersed lymphoma from a λ-Myc mouse (ID 2749).
In fact, RVX2135 doubled both the median and overall survival of mice carrying 2749 lymphoma, when compared to vehicle-treated controls.
Dr Nilsson and his colleagues then investigated the mechanism behind these effects. They found that RVX2135 induces a complex transcriptional program without specifically inactivating transgenic Myc transcription.
By examining the genes induced by BET inhibition, the researchers discovered that RVX2135 activates the same genes as those activated by HDAC inhibitors.
So the team tested the HDAC inhibitor vorinostat in combination with RVX2135. And the combination increased survival in mice with 2749 lymphoma, when compared to either inhibitor alone.
“It was also possible to reduce the dose of HDAC inhibitors when used in combination with RVX2135, and this reduced adverse effects,” Dr Nilsson said.
“We see this as a breakthrough in the clinical development of this type of treatment. [W]e believe that the prospects for success with combination treatments are good.”