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American Association of Cancer Research: Only the beginning


Jon and I are attending the American Association for Cancer Research this weekend. While most of the information being disseminated isn't ready for clinical use, there are several topics we're following that may be of interest to you. This morning we attended a press briefing that included information on promising treatments in clinical trials. The data presented included a very early phase I trial combining two investigational drugs, a promising therapy for a rare type of inherited basal cell carcinoma (skin cancer), an update on a novel way to test new drug therapies, and if a hypertension drug could help prevent lung cancer in former smokers.A phase Ib study looked at two drugs that target two different pathways -- MEK and pan-PI3K –- had intriguing results. The treatment was tested in a variety of cancers, including melanoma and lung cancer, and found that by targeting two cancer pathways at the same time, it created a synergistic effect and inhibited "cross talk" between the two pathways. We discussed the concept of targeting two pathways in "A New Era" as it relates to breast cancer. In essence, if you block one cancer growth pathway, the cancer could potentially begin using a different pathway. Side effects of the combination included diarrhea and rash, but most incidences were mild. The study is ongoing. Basal cell carcinoma is a common type of skin cancer that is seldom life-threatening; however, there is a rare inherited type of the disease called basal cell nevus syndrome (BCNS) that presents as hundreds of basal cell carcinoma lesions all over the body. The trial showed the drug works rapidly and shrinks existing cancers, but has unsettling side effects, including hair loss, muscle cramps, and taste and weight loss. Researchers also admitted they do not yet know long-term results. It doesn't appear the drug will have a clinical use in common cases of basal cell carcinoma since patients with one or two tumors can be effectively treated with surgery alone. But for those patients with BCNS, it could become a useful therapy.The BATTLE (Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination) trial is unique in that it has an adaptive clinical trial design. We covered the BATTLE trial at last year's AACR, including that scientists are testing several drugs, each designed to target a particular cancer pathway: Tarceva (erlotinib) with or without Targretin (bexarotene), Nexavar (sorafenib) and Zactima (vandetanib). Patients with advanced non-small cell lung cancer were assigned a drug, and their tumors were assayed for certain biomarkers. As the researchers evaluated what appeared to work, they changed strategy: Patients with known tumor biomarkers were treated with the drug that had worked best for earlier patients with similar biomarkers. This year, John Heyworth, MD, PhD, at M.D. Anderson's department of thoracic/head and neck oncology, says they found gene expression signatures that might be predictive in patients with normal EGFR (epidermal growth factor receptor). Currently, we have a limited ability to match the right drug with the right patient, he says. While patients with an EGFR mutation are typically treated with drugs that target that mutation, those patients only account for about 12 percent of NSCLC patients. However, there are some cases where patients who do not have the mutation also benefit from EGFR inhibitors, such as Tarceva. Unfortunately, we don't know how to identify those patients, he says, which is why they are attempting to develop markers for these patients with normal EGFR. Heyworth announced that they had developed a gene expression signature that could indicate treatment benefit in patients with normal EGFR, including identifying two genes that could be potential drug targets. Ultimately, 83 percent of patient with the signature responded to Tarceva compared with no patients who did not have the signature. Both sets of signatures will be tested in the follow up BATTLE 2 trial.The chemoprevention study in lung cancer looked at a hypertension drug, Iloprost, and examined whether it could reduce the incidence of bronchial hyperplasia, which could be a biomarker for lung cancer. Researchers don't yet know if the drug reduces the risk of lung cancer, though. It was interesting in that the effect was significant in former smokers, but not current smokers.The final study explained that while estrogen-receptor positive breast cancer is common there is a subset of these cancers that are resistant to hormone therapy. Researchers sequenced whole genomes of 50 of these ER-positive, hormone-resistant cancers, finding three common gene mutations--PIK3CA, TP53 and MAP3Ki. There were also about 20 other mutated genes that kept popping up. Researchers discovered that many of these other mutated genes they found could be targeted by already approved drugs.While all of these studies appear promising, the research is still very early. Most of these studies, in addition to the others presented here at AACR, are usually the first steps and lay the groundwork for later research.

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