**EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy** Paez, J. G. et al. (2004) and Lynch, T. J. et al. (2004) identified point or deletion mutations in the epidermal growth factor receptor (EGFR) that predict responsiveness to the tyrosine kinase inhibitor gefitinib. Tumour biopsies from patients with gefitinib-responsive lung cancer often carried these mutations, while none were found in non-responders. The mutations are located in the ATP-binding pocket of the tyrosine kinase domain and are associated with increased sensitivity to gefitinib. **Structures of HIV-1 RT-DNA Complexes Before and After Incorporation of Tenofovir** Tuske, S. et al. (2004) compared the structures of HIV-1 reverse transcriptase (RT) bound to tenofovir, an anti-AIDS drug. The study explains the low resistance of HIV to tenofovir by showing that mutations that could reduce tenofovir incorporation would also impair RT function. Additionally, incorporated tenofovir can escape the 'correction' activity of RT by adopting multiple conformations, moving out of the active site. **Determination of the Role of Human RNase H1 in the Pharmacology of DNA-like Antisense Drugs** Wu, H. et al. (2004) demonstrated that RNase H1 is crucial for the effects of DNA-like antisense oligonucleotides (ASOs). They found that altering the expression levels and cellular activity of RNase H1 significantly impacted the activity of DNA-like ASOs. The study also suggests the presence of other RNase H enzymes in mammalian cells that contribute to ASO activity. **Overexpression of the *c-MYC* Proto-oncogene and Its Therapeutic Rescue** Hurley and colleagues reported a unique mutational mechanism for overexpression of *c-MYC* in human colorectal cancers. They identified G-quadruplex mutations in the *c-MYC* promoter that destabilize the G-quadruplex structure, leading to increased *c-MYC* expression. Treatment with the cationic porphyrin compound TMPyP4, which stabilizes the G-quadruplex, reduced *c-MYC* levels. The study found that in cells with lower levels of NM23-H2, a protein that activates *c-MYC* transcription, stabilization by TMPyP4 was enhanced. This suggests a novel approach to modulating *c-MYC* expression and potentially reversing the consequences of mutational events in this gene.**EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy** Paez, J. G. et al. (2004) and Lynch, T. J. et al. (2004) identified point or deletion mutations in the epidermal growth factor receptor (EGFR) that predict responsiveness to the tyrosine kinase inhibitor gefitinib. Tumour biopsies from patients with gefitinib-responsive lung cancer often carried these mutations, while none were found in non-responders. The mutations are located in the ATP-binding pocket of the tyrosine kinase domain and are associated with increased sensitivity to gefitinib. **Structures of HIV-1 RT-DNA Complexes Before and After Incorporation of Tenofovir** Tuske, S. et al. (2004) compared the structures of HIV-1 reverse transcriptase (RT) bound to tenofovir, an anti-AIDS drug. The study explains the low resistance of HIV to tenofovir by showing that mutations that could reduce tenofovir incorporation would also impair RT function. Additionally, incorporated tenofovir can escape the 'correction' activity of RT by adopting multiple conformations, moving out of the active site. **Determination of the Role of Human RNase H1 in the Pharmacology of DNA-like Antisense Drugs** Wu, H. et al. (2004) demonstrated that RNase H1 is crucial for the effects of DNA-like antisense oligonucleotides (ASOs). They found that altering the expression levels and cellular activity of RNase H1 significantly impacted the activity of DNA-like ASOs. The study also suggests the presence of other RNase H enzymes in mammalian cells that contribute to ASO activity. **Overexpression of the *c-MYC* Proto-oncogene and Its Therapeutic Rescue** Hurley and colleagues reported a unique mutational mechanism for overexpression of *c-MYC* in human colorectal cancers. They identified G-quadruplex mutations in the *c-MYC* promoter that destabilize the G-quadruplex structure, leading to increased *c-MYC* expression. Treatment with the cationic porphyrin compound TMPyP4, which stabilizes the G-quadruplex, reduced *c-MYC* levels. The study found that in cells with lower levels of NM23-H2, a protein that activates *c-MYC* transcription, stabilization by TMPyP4 was enhanced. This suggests a novel approach to modulating *c-MYC* expression and potentially reversing the consequences of mutational events in this gene.