Tracking Resistance to Cancer Therapies Without Tumor Access


Clinicians would like to be able to monitor whether a cancer patient’s tumor has acquired a resistance mutation as a result of targeted therapy. Knowing early if resistance has developed would allow patients to switch therapies and to curb tumor growth. But taking repeated tumor samples is problematic for many reasons. Biopsies are invasive and some tumors are inaccessible. Another issue is that tumors are mosaics of many different types of cells that are constantly evolving—since biopsies take time in the clinic and only sample a small part of a tumor, they may also not be representative of what is going on with the biology of the entire tumor mass. Continue reading…


Targeting Non-BRAF Mutations in Melanoma to Address BRAF Inhibitor Therapy Resistance


BRAF-mutated metastatic melanoma can be treated with the U.S. Food and Drug Administration (FDA)-approved drug vemurafenib, an oral therapy that targets the V600E mutation in the BRAF protein. Another BRAF inhibitor, dabrafenib, has been filed with the FDA for treatment of the same patient population. BRAF inhibition results in rapid shrinkage of tumors for the majority of BRAF-mutated melanoma patients. But while treatment with a BRAF inhibitor alone results in tumor shrinkage in the short-term, patients’ tumors begin to grow again, typically 6 to 7 months after starting treatment. Continue reading…


Genetically Modified Cold Sore Virus Shows Promise in Melanoma


A new immunotherapy known as talimogene laherparepvec (T-VEC), or Ovcovex GM-CSF, has shown the ability to shrink advanced melanoma tumors. T-VEC is a genetically modified version of herpes simplex virus type 1, the virus that causes cold sores. T-VEC was also engineered to produce GM-CSF (granulocyte-macrophage colony-stimulating factor), a protein that stimulates the immune system.  Amgen, the California-based biopharmaceutical company that is developing the experimental cancer therapy, announced on March 19 that T-VEC had shown positive results in an advanced melanoma clinical trial. Continue reading…


Immunotherapies Take Center Stage in Treatment of Metastatic Melanoma


The promise of immunotherapy is coming to fruition with therapeutic advances in melanoma. In 1998, high-dose interleukin-2 (HD IL-2) became the first U.S. Food and Drug Administration (FDA)-approved immunotherapy for metastatic melanoma. But HD IL-2 is severely toxic and benefits only a small minority of patients. In 2011, ipilimumab became the second immunotherapy approved for metastatic melanoma. Continue reading…


Video: Cancer Survivor Sharon Anderson on the Importance of Patient-Donated Data


In 2002, Sharon Anderson was diagnosed with a rare form of cancer called leiomyosarcoma (LMS). She joined an online discussion group to explore treatment options with other LMS patients, and tried a drug typically used for breast cancer. Her treatment was successful. In the video above, she tells us how she helped fellow LMS patients gather data about their own tumors and share it with a researcher. The resulting cancer vaccine is now in a phase I clinical trial. Continue reading…


Revamping the Way Cancer Vaccines Are Made Could Boost Their Efficacy


While not as toxic as other therapy approaches, cancer vaccines have also not been very effective. Despite many attempts by researchers, the only therapeutic cancer vaccine that has been approved by the Food and Drug Administration (FDA) is sipuleucel-T (Provenge), which is approved specifically for men with metastatic prostate cancer. Continue reading…


Researchers Develop Microscopic Cantilever to Detect BRAF Mutations


Researchers have developed a sensitive method to directly detect mutations in the BRAF gene without amplifying a DNA or RNA sample. Professor Christoph Gerber of the Swiss Nanoscience Institute at the University of Basel, Switzerland; Donata Rimoldi of the Ludwig Institute for Cancer Research in Lausanne, Switzerland; and their respective colleagues developed a nanotechnology approach to detect the mutation in RNA from melanoma cells with the help of a microscopic cantilever. Continue reading…


Treatment of Metastatic Melanoma—Evolution from Monotherapy to Combination Therapies


The most prevalent genetic alteration identified in melanoma is a mutation in the BRAF gene that increases the activity of the BRAF protein. As many as 50% of melanoma tumors express a BRAF mutation; the most common is the V600E mutation, found in 80% to 90% of BRAF-mutant patients. The first targeted therapy developed for melanoma, vemurafenib, directly inhibits the BRAF protein. In August 2011, the Food and Drug Administration (FDA) approved vemurafenib for treatment of metastatic melanoma with the BRAF V600E mutation. Now, a second BRAF inhibitor, dabrafenib, and a MEK inhibitor, trametinib, have been filed with the FDA for treatment of metastatic melanoma and several late-stage dabrafenib plus trametinib combination trials are underway. Continue reading…


Treating BRAF-Mutated Melanoma: Tough Choices for Clinicians and Patients


Where there were no treatment options for metastatic melanoma patients in the past, there are now several. Prior to 2010, only two treatments were approved: the chemotherapy drug dacarbazine and recombinant human interleukin 2 (IL-2) immunotherapy. Neither was effective in providing durable responses or led to an improvement in overall survival.

But now, the immunotherapy antibody ipilimumab and the targeted oral therapy vemurafenib, a BRAF inhibitor, have been shown to improve overall survival. Both were approved by the Food and Drug Administration (FDA) in 2011. Continue reading…