MUTATIONS IN SOLID TUMOR MALIGNANCIES

Oncogene Mutations in Cancer Therapy
David Sidransky, MD

Dr. Sidransky introduced the topic of mutational analysis in solid tumors and why it is important to screen for these mutations. He also highlighted the need for model systems, such as tumorgrafts, that can be used to screen a patient’s tumor sample for both biomarkers and which therapy or combination of therapies might be most effective to treat a particular patient. View this presentation

Toward Personalized Therapy for Lung Cancer
Roy S. Herbst, M.D., Ph.D.

Dr. Herbst provided an updated summary on the use of targeted therapies in the treatment of NSCLC and the results of several recent clinical trials. He also described an innovative approach to biomarker identification and patient selection that is being used at MD Anderson called BATTLE (Biomarker-based Approaches of Targeted Therapy for Lung Cancer Elimination). This approach interrogates 4 major signaling pathways known to be deregulated in NSCLC to guide patient specific treatment options individualized for their cancer.
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Activating Mutations in EGFR and Response to Targeted Therapy in Lung Cancer
Pasi A. Jänne, M.D.,Ph.D.

Dr. Jänne provided an update on EGFR inhibitors in the treatment of NSCLC and presented analyses from several recent trials. He also discussed the role of activating EGFR mutations as biomarkers to select patients for anti-EGFR targeted therapies and why it is important to select patients based on genotype (confirming the presence of an activating EGFR mutation by genotyping) and not phenotype (treating all non-smokers with NSCLC with anti-EGFR therapies because this group often has activating EGFR mutations). However, non-smokers without the mutation are still unlikely to benefit from anti-EGFR directed therapy.
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Ras Mutations – Implications of Response to Anti-EGFR Targeted Therapies
Sabine Tejpar, MD, PhD

Dr. Tejpar discussed the criteria that need to be met for a biomarker to be truly predictive. She then discussed much of the current clinical data presented at the meeting on the correlation between KRAS mutations and lack of clinical response to anti-EGFR targeted therapies. She also highlighted the importance of accurately performing KRAS genotyping and reviewed current Real-Time PCR based technologies for KRAS genotyping. She discussed whether KRAS is ready for “prime time” as a predictive biomarker for anti-EGFR
targeted therapies. View this presentation

Genetic Predictors of MEK-dependence
David Solit, MD

Dr. Solit broadened the topic of mutations in solid tumors by discussing his work with MEK inhibitors and the impact of analyzing for BRAF mutations as a possible predictive marker for MEK inhibitors. MEK inhibitors have shown activity in many tumor cell lines with BRAF mutations. He also discussed how BRAF mutations could also play a role in selecting patients for anti-EGFR targeted therapies, although much clinical analysis still needs to be performed to resolve this issue. Dr. Solit stressed the need to more broadly genotype patients at the time of diagnosis for mutations such as BRAF, even though they are not found as frequently as KRAS, in order to truly individualize patient therapy. View this presentation