Post by Max on Jul 25, 2005 9:19:18 GMT -5
(Ro)accutane induced effects related to effects from other substances from Hoffman la Roche´s product line
Some mechanisms in hoffman la Roche´s product line may be directly recognizable as partial effects that are induced from (Ro)accutane. A relation to research done on (Ro)accutane induced effects can not be excluded. Therefore, research on (Ro)accutane induced effects may be beneficial in clarifying effects of other products marketed by Hoffman la Roche and vice versa. However, other common characteristics include that the mechanism of action seldom is fully known, if known at all, and that the selectivity is limited. For some substances there is even a lack of declared metabolic pathways.
(Ro)accutane (isotreinoin)
Non-selective, highly toxic retinoid. Non-defined general and wide extensive effects.
Xenical (orlistat)
Non-selective lipoprotein lipase inhibitor. Inserts its action by forming covalent bonds with serine residues [0]. The lipoprotein lipase is found to be inhibited by 13-cis-RA [x].
Naprosyn (naproxen)
NSAID, non-selective prostaglandin syntethase (PGHS) inhibitor [0]. PGHS is involved in the catabolic pathways of 13-cis-RA [1].
PGHS-catalyzed oxidation of RA and (13Z)-RA was shown to form free radical adducts, using electron spin resonance (ESR) spin trapping techniques and 5-phenyl-4-penten-1-yl hydroperoxide (PPHP) or 13-hydroperoxy-9-cis-11-trans-octadecadienoic acid (13-OOH-18:2) as hydroperoxide substrates [1].
Herceptin (trastuzumab)
Anti-Her2 monoclonal antibody. Her2 positive breast cancer. Under evaluation.
Lack of markers
Although many different anticancer drugs appear to mediate tumor regression by inducing apoptosis, there is currently no consistent evidence that any of the molecules implicated in this process can be used as predictive markers [4].
It is not known when and in which patients Herceptin may be beneficial, due to a lack of accurate predictive markers.
Resistance to Herceptin common; higher rates of metastases found in patients exposed to Herceptin; possibly due to EGF-R receptor malfunction over time
The majority of patients who achieve an initial response to Herceptin generally acquire resistance within one year [3]. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment [2].
Contradictions exist. It is not known why a resistance to Herceptin occurs frequently. There is a lack of data showing what aquired resistance means in terms of survival and increased/decreased development of metastases. Herceptin treatment causes c-erbB2 phosphorylation of Y877 and Y1248 [6]. The role of overexpression of the EGF-R receptor family in cancer development is not fully understood. The role of lack of EGF-R expression/aquired resistance is not fully understood.
Questions to be answered in the future include if there is an optimal rate of HER2 expression and optimal rate of EGFR function (neither overexpressed, nor underexpressed) for the most beneficial cancer treatment?
Some mechanisms in hoffman la Roche´s product line may be directly recognizable as partial effects that are induced from (Ro)accutane. A relation to research done on (Ro)accutane induced effects can not be excluded. Therefore, research on (Ro)accutane induced effects may be beneficial in clarifying effects of other products marketed by Hoffman la Roche and vice versa. However, other common characteristics include that the mechanism of action seldom is fully known, if known at all, and that the selectivity is limited. For some substances there is even a lack of declared metabolic pathways.
(Ro)accutane (isotreinoin)
Non-selective, highly toxic retinoid. Non-defined general and wide extensive effects.
Xenical (orlistat)
Non-selective lipoprotein lipase inhibitor. Inserts its action by forming covalent bonds with serine residues [0]. The lipoprotein lipase is found to be inhibited by 13-cis-RA [x].
Naprosyn (naproxen)
NSAID, non-selective prostaglandin syntethase (PGHS) inhibitor [0]. PGHS is involved in the catabolic pathways of 13-cis-RA [1].
PGHS-catalyzed oxidation of RA and (13Z)-RA was shown to form free radical adducts, using electron spin resonance (ESR) spin trapping techniques and 5-phenyl-4-penten-1-yl hydroperoxide (PPHP) or 13-hydroperoxy-9-cis-11-trans-octadecadienoic acid (13-OOH-18:2) as hydroperoxide substrates [1].
Herceptin (trastuzumab)
Anti-Her2 monoclonal antibody. Her2 positive breast cancer. Under evaluation.
Lack of markers
Although many different anticancer drugs appear to mediate tumor regression by inducing apoptosis, there is currently no consistent evidence that any of the molecules implicated in this process can be used as predictive markers [4].
It is not known when and in which patients Herceptin may be beneficial, due to a lack of accurate predictive markers.
Resistance to Herceptin common; higher rates of metastases found in patients exposed to Herceptin; possibly due to EGF-R receptor malfunction over time
The majority of patients who achieve an initial response to Herceptin generally acquire resistance within one year [3]. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment [2].
Contradictions exist. It is not known why a resistance to Herceptin occurs frequently. There is a lack of data showing what aquired resistance means in terms of survival and increased/decreased development of metastases. Herceptin treatment causes c-erbB2 phosphorylation of Y877 and Y1248 [6]. The role of overexpression of the EGF-R receptor family in cancer development is not fully understood. The role of lack of EGF-R expression/aquired resistance is not fully understood.
Questions to be answered in the future include if there is an optimal rate of HER2 expression and optimal rate of EGFR function (neither overexpressed, nor underexpressed) for the most beneficial cancer treatment?