Deregulation of eukaryotic translation machinery has been implicated in several malignancies. Eukaryotic translation takes place through both Cap-dependent and Cap-Independent mechanisms. 5'Cap is a modified guanosine attached to the 5' end of eukaryotic mRNA which serves as a binding site for the initiation factor eIF4E. The Cap dependent mechanism, which is responsible for translation of 95-97% of all cellular mRNA involves scanning of mRNA for start codon AUG nearest to 5'cap. A mathematical model of cap-mediated translation initiation was formed which consists of the following main steps (1) Formation of 40S ribosomal sub-unit and ternary complex; (2) ATP dependent activation of mRNA and it's binding to the 40S subunit to form 48S complex; (3) Scanning of mRNA for start codon AUG and (4) joining of the 48S and 60S complex to form the 80S initiation complex. Positive regulation by TOR kinase was modeled by including the PI3K/PTEN/Akt dependent phosphorylation of eIF-BP by TOR kinase. The model parameters in a system of 60 interactions with 53 species were chosen to mimic physiological time-profiles (called the nominal set of parameters) for species in the initiation pathway and the system of equations was solved using ODE15s routine in MATLAB v7.01 (The Mathworks, Natick MA). Sensitivity analysis was also performed on the system to identify important or fragile reactions and species in the model. Three different numerical methods were used to solve the sensitivity equations over a family of 500 random parameter sets formed by perturbing the nominal set of parameters by upto 2 orders of magnitude, a forward finite difference method, a third-order Backward Difference Method and the direct solution of the sensitivity equations using ODE15s. Overall State Sensitivity Coefficients (OSSC), calculated using each of these methods, were compared to arrive at a conscious estimate of points of fragility in Cap mediated translation. Sensitivity analysis predicted that 7 out of the 10 top sensitive parameters involve the PI3K/PTEN/Akt dependent phosphorylation of eIF-BP by TOR kinase. These findings are consistent with Bjornsti et al., who report that activation of TOR kinase by the Akt pathway is responsible for formation of many human carcinomas, e.g., thyroid carcinoma, colon carcinoma and breast cancer. Thus, sensitivity analysis in combination with mechanistic modeling of translation initiation was able to correctly discern sensitive mechanisms in the TOR kinase activation pathway whose deregulation is linked with several human cancers.