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Introduction

Celebrating Milestones in Oncology: Multiple Myeloma

Among the greatest success stories in the history of advances in cancer treatment is the extraordinary progress over the last 4 decades in the treatment of multiple myeloma...

The introduction of thalidomide, an immunomodulatory agent (IMiDs), in the late 1990s, which improved both longer progression-free and overall survival in patients, was followed in rapid succession by the introduction of lenalidomide, a thalidomide derivative; proteasome inhibitors, including bortezomib, carfilzomib, and ixazomib; pomalyst, a thalidomide analogue, in combination with the steroid dexamethasone; daratumumab, an anti-CD38 monoclonal antibody; pan-HDAC inhibitors, including panobinostat, vorinostat, belinostat, and romidepsin; elotuzumab, an anti-SLAMF7 inhibitor; and belantamab mafodotin, an antibody-drug conjugate.

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Dec 1 2012

Oct 2015

Mar 2018

December 1, 2012

Decoding the Genetic Blueprint of Cancer Cells...

Among the greatest success stories in the history of advances in cancer treatment is the extraordinary progress over the last 4 decades...

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October 25, 2015

A Snapshot of Early Immunotherapy

Over the past several years, immunotherapy has had a renaissance of sorts, emerging as one of the most active areas in cancer research. For instance, we have seen the therapeutic promise of disrupting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) immune checkpoints in cancer, which has encouraged large clinical studies in this and other promising investigations in immune therapy.

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March 25, 2018

Cabozantinib Therapy Shows Activity in Differentiated Thyroid Cancer

Cabozantinib (Cometriq) has demonstrated significant activity in the first-line setting for radioiodine-refractory differentiated thyroid carcinoma, according to data from a single-site phase II trial presented at the 2018 Multidisciplinary Head and Neck Cancers Symposium.1 Treatment with cabozantinib resulted in a 54% response rate and an 80% clinical benefit rate, meeting the primary endpoint of the study. Cabozantinib was also well tolerated, the authors noted, with mostly grade 1 and 2 adverse events and no unexpected toxicities identified.

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< Decoding the Genetic Blueprint of Cancer Cells: Findings in Multiple Myeloma and Breast Cancer
June 15, 2012
Jo Cavallo

Advances in next-generation DNA sequencing technologies are allowing scientists to decipher the whole genome or whole exome (ie, the coding region of the genome) of cancer specimens more quickly and inexpensively than ever before. And the results are revealing genes that had not previously been associated with cancer as well as multiple genetic mutations that disrupt common pathways and trigger cancer-related changes in a cell.

Findings in Multiple Myeloma

Todd R. Golub, MD, Director of the Cancer Program at the Broad Institute, Charles A. Dana Investigator in Human Cancer Genetics at Dana-Farber Cancer Institute, is a coauthor of the first large-scale study to compare the entire genomes of malignant cells and normal cells from 38 patients with multiple myeloma. Dr. Golub and co-investigators at the Broad Institute and Dana-Farber Cancer Institute, Boston, found mutations in the nuclear factor (NF)-kappaB pathway, an important transcriptional regulator in multiple myeloma. Although researchers had suspected that this pathway was involved in the development of the disease, they did not understand the chain of events that turned the pathway on. The study, published last year in the journal Nature,1 found that 11 different genes involved in the NF-kappaB pathway were altered in at least one tumor sample.

In addition, mutations were found in genes that are involved in two cellular processes in normal cell function: RNA processing and protein folding. About half of the multiple myeloma samples sequenced had defects in one or more of these genes, including FAM46C, which had never before been linked to cancer. Another surprising discovery was that a small number of multiple myeloma patients (just 4%) had BRAF V600E gene mutations—the same mutation found in some types of melanoma and colon cancer, which had not previously been associated with the development of multiple myeloma.

A Snapshot of Early Immunotherapy
October 25, 2015
Ronald Piana

Over the past several years, immunotherapy has had a renaissance of sorts, emerging as one of the most active areas in cancer research. For instance, we have seen the therapeutic promise of disrupting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) immune checkpoints in cancer, which has encouraged large clinical studies in this and other promising investigations in immune therapy. And although immunotherapy’s potential is now energizing the oncology community, this pioneering line of cancer treatment has been around, in one form or another, for centuries.

The First Clinical Trial

The early paradigm that shaped the development of most cancer therapies, until recently, was grounded in the observations based on infectious disease. And those observations began early in human history. Thucydides, a prominent Greek historian, first recorded resistance to a specific disease in 430 B.C. After the devastating plague of Athens, Thucydides, a survivor himself, noticed that the disease never attacked the same survivor twice. In his writings, he postulated that those surviving the plague had acquired some uncanny form of resistance to the disease, which is one of the first known observations of the immune system in action.

The first recorded immunotherapy trial was conducted in Newgate Prison, London, in 1721. During her travels, the Princess of Wales had heard of miraculous resistance following deliberate or accidental exposure to smallpox exposure. Fearing her children might contract the dreaded disease, she granted Charles Maitland, MD, permission to perform a trial on six condemned prisoners. The subjects were infected with pus from individuals who had smallpox, and then he exposed them to active cases. All of the prisoners on the “smallpox trial” survived; out of gratitude for their participation, they were released from prison 1 month later.

Cabozantinib Therapy Shows Activity in Differentiated Thyroid Cancer
March 25, 2018
Chase Doyle

Cabozantinib (Cometriq) has demonstrated significant activity in the first-line setting for radioiodine-refractory differentiated thyroid carcinoma, according to data from a single-site phase II trial presented at the 2018 Multidisciplinary Head and Neck Cancers Symposium.1 Treatment with cabozantinib resulted in a 54% response rate and an 80% clinical benefit rate, meeting the primary endpoint of the study. Cabozantinib was also well tolerated, the authors noted, with mostly grade 1 and 2 adverse events and no unexpected toxicities identified.

“This phase II trial showed that cabozantinib is an active agent for radioiodine-refractory differentiated thyroid carcinoma in the first-line setting and merits additional study in a large, multicenter phase III trial,” said Marcia S. Brose, MD, PhD, Associate Professor in the Department of Otorhinolaryngology: Head and Neck Surgery and Director of the Center for Rare Cancers and Personalized Therapy at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

As Dr. Brose reported, in 2017 there were more than 56,000 new cases of thyroid cancer diagnosed in the United States, and in approximately 5% to 15% of these cases, the disease becomes refractory to radioiodine. Although the recent approval of two kinase inhibitors by the U.S. Food and Drug Administration (FDA) has helped to increase progression-free survival, the responses are not durable, and toxicities may limit efficacy.

“Sorafenib [Nexavar] and lenvatinib [Lenvima] are used sequentially to improve the progression-free interval for these patients, but patients ultimately progress and need more treatment options,” said Dr. Brose.

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