Paloma Pharmaceuticals, Inc. Published Paper in British Journal of Cancer
Jamaica Plain, MA, Feb. 24, 2009 -- Paloma Pharmaceuticals, Inc. today announced it has
published a paper on the Company’s PI3K/Akt/mTOR inhibitor Palomid 529 (P529) in the
British Journal of Cancer.
P529 is a non-steroidal, synthetic, small molecule anti-tumor agent created through computational design, synthetic and medicinal chemistry, the result of three generations of Palomid design work. Palomid’s broad activity as an anti-tumor agent is shown to reside in its ability to target and inhibit the PI3K/Akt/mTOR signal transduction pathway as a dual TORC1/TORC2 inhibitor.
Work constituting the British Journal of Cancer paper, “The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer”, was conducted by the laboratory of Dr. Alfonso Calvo of the Division of Oncology, Center for Applied Medical Research (CIMA). University of Navarra, Pamplona, Spain.
“This paper is brings out some very exciting findings of Palomid 529 our flagship oncologic agent. Palomid 529 is shown to synergize with radiation therapy both on tumor cells in vitro and in an in vivo animal model of prostate cancer. It also indicates a potential problem in radiation therapy. When radiation therapy is given to patients it is necessary to kill all cancer cells. If all cancer cells are not killed, it is possible that radiation could actually induce events which could accelerate cancer growth. When tumor cells are irradiated they can up-regulate PI3K/Akt/mTOR pathway in existing cancer cells and induce both their growth and secretion of VEGF which could then induce angiogenesis providing the tumor with nutritive blood flow. Such a result is shown in this paper in that when prostate tumor cells were irradiated both Akt phosphorylation and VEGF synthesis was observed to rise in the tumor cells. Furthermore of great interest is that when Palomid 529 is added to the prostate tumor cells this phosphorylation of Akt and VEGF synthesis is considerably reduced. Such a result is important in that not only does Palomid 529 inhibit tumor growth itself but also may prevent auxiliary tumor growth when radiation does not entirely kill all cancer cells”, said Dr. Sherris.
About the PI3K/Akt/mTOR Pathway
The PI3K/Akt/mTOR pathway has been implicated in a wide variety of biological responses and is considered a major therapeutic target in cancer. Activation of this signaling pathway, via direct or indirect mutagenic events, is common in many types of human cancer resulting in deregulation of PI3K/Akt/mTOR pathway in cancer. Thus, agents capable of inhibiting the PI3K/Akt/mTOR pathway are attractive targets for therapeutic intervention in cancer. Central within the signalling pathway are two distinct protein complexes, one of which regulates growth through the signal transduction protein S6K, TORC1, and the other that regulates cell survival through Akt, TORC2. These complexes define both rapamycin-sensitive and insensitive branches of the PI3K/Akt/mTOR pathway. Inhibition of the TORC2 pathway suppresses the formation of tumors driven by the loss of the PTEN tumor suppressor, a gene which when lost contributes to carcinogenicity. Inhibitors of TORC2 may then have beneficial effects as anticancer agents without toxicity to normal tissues since loss of TORC2 through genetic alteration does not appear to affect normal tissue. TORC1 antagonists as rapamycin and other such rapalogs have shown activity in both animal models of cancer and in human clinical trials. As inhibition of both TORC1 and TORC2 should result in more complete inhibition of PI3K/Akt/mTOR signaling up-regulated in cancer, dual inhibitors are of active interest for pharmaceutical development.
About Paloma Pharmaceuticals
Paloma Pharmaceuticals, Inc. is an early stage drug development company focusing on cancer, ocular diseases (macular degeneration and diabetic retinopathy), arthritis, fibrotic diseases (pulmonary fibrosis) endometriosis, osteoporosis and skin diseases (psoriasis and atopic dermatitis). Paloma owns the intellectual property relating to a library of novel, proprietary, small molecule drugs created through an integrated design platform incorporating proprietary, customized and industry standard computational tools that has therapeutic potential for the treatment of the foregoing diseases.
SOURCE Paloma Pharmaceuticals, Inc.
http://www.palomapharma.com.
P529 is a non-steroidal, synthetic, small molecule anti-tumor agent created through computational design, synthetic and medicinal chemistry, the result of three generations of Palomid design work. Palomid’s broad activity as an anti-tumor agent is shown to reside in its ability to target and inhibit the PI3K/Akt/mTOR signal transduction pathway as a dual TORC1/TORC2 inhibitor.
Work constituting the British Journal of Cancer paper, “The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer”, was conducted by the laboratory of Dr. Alfonso Calvo of the Division of Oncology, Center for Applied Medical Research (CIMA). University of Navarra, Pamplona, Spain.
“This paper is brings out some very exciting findings of Palomid 529 our flagship oncologic agent. Palomid 529 is shown to synergize with radiation therapy both on tumor cells in vitro and in an in vivo animal model of prostate cancer. It also indicates a potential problem in radiation therapy. When radiation therapy is given to patients it is necessary to kill all cancer cells. If all cancer cells are not killed, it is possible that radiation could actually induce events which could accelerate cancer growth. When tumor cells are irradiated they can up-regulate PI3K/Akt/mTOR pathway in existing cancer cells and induce both their growth and secretion of VEGF which could then induce angiogenesis providing the tumor with nutritive blood flow. Such a result is shown in this paper in that when prostate tumor cells were irradiated both Akt phosphorylation and VEGF synthesis was observed to rise in the tumor cells. Furthermore of great interest is that when Palomid 529 is added to the prostate tumor cells this phosphorylation of Akt and VEGF synthesis is considerably reduced. Such a result is important in that not only does Palomid 529 inhibit tumor growth itself but also may prevent auxiliary tumor growth when radiation does not entirely kill all cancer cells”, said Dr. Sherris.
About the PI3K/Akt/mTOR Pathway
The PI3K/Akt/mTOR pathway has been implicated in a wide variety of biological responses and is considered a major therapeutic target in cancer. Activation of this signaling pathway, via direct or indirect mutagenic events, is common in many types of human cancer resulting in deregulation of PI3K/Akt/mTOR pathway in cancer. Thus, agents capable of inhibiting the PI3K/Akt/mTOR pathway are attractive targets for therapeutic intervention in cancer. Central within the signalling pathway are two distinct protein complexes, one of which regulates growth through the signal transduction protein S6K, TORC1, and the other that regulates cell survival through Akt, TORC2. These complexes define both rapamycin-sensitive and insensitive branches of the PI3K/Akt/mTOR pathway. Inhibition of the TORC2 pathway suppresses the formation of tumors driven by the loss of the PTEN tumor suppressor, a gene which when lost contributes to carcinogenicity. Inhibitors of TORC2 may then have beneficial effects as anticancer agents without toxicity to normal tissues since loss of TORC2 through genetic alteration does not appear to affect normal tissue. TORC1 antagonists as rapamycin and other such rapalogs have shown activity in both animal models of cancer and in human clinical trials. As inhibition of both TORC1 and TORC2 should result in more complete inhibition of PI3K/Akt/mTOR signaling up-regulated in cancer, dual inhibitors are of active interest for pharmaceutical development.
About Paloma Pharmaceuticals
Paloma Pharmaceuticals, Inc. is an early stage drug development company focusing on cancer, ocular diseases (macular degeneration and diabetic retinopathy), arthritis, fibrotic diseases (pulmonary fibrosis) endometriosis, osteoporosis and skin diseases (psoriasis and atopic dermatitis). Paloma owns the intellectual property relating to a library of novel, proprietary, small molecule drugs created through an integrated design platform incorporating proprietary, customized and industry standard computational tools that has therapeutic potential for the treatment of the foregoing diseases.
SOURCE Paloma Pharmaceuticals, Inc.
http://www.palomapharma.com.