Personalized Medicine Best Way to Treat Cancer, Study Argues

“Assessing the route to cancer on a case-by-case basis might make more sense than basing a patient’s cancer treatment on commonly disrupted genes and pathways, a new study indicates. “This paper argues for the importance of personalized medicine, where we treat each person by looking for the etiology of the disease in patients individually,” said the lead author. “The findings have ramifications on how we might best optimize cancer treatments as we enter the era of targeted gene therapy.”


Personalized Medicine Best Way to Treat Cancer, Study Argues

“Assessing the route to cancer on a case-by-case basis might make more sense than basing a patient’s cancer treatment on commonly disrupted genes and pathways, a new study indicates. “This paper argues for the importance of personalized medicine, where we treat each person by looking for the etiology of the disease in patients individually,” said the lead author. “The findings have ramifications on how we might best optimize cancer treatments as we enter the era of targeted gene therapy.”


Personalized Medicine Best Way to Treat Cancer, Study Argues

“Assessing the route to cancer on a case-by-case basis might make more sense than basing a patient’s cancer treatment on commonly disrupted genes and pathways, a new study indicates. “This paper argues for the importance of personalized medicine, where we treat each person by looking for the etiology of the disease in patients individually,” said the lead author. “The findings have ramifications on how we might best optimize cancer treatments as we enter the era of targeted gene therapy.”


Overcoming Resistance to BRAF Inhibitors May Take Two More Drugs

We already knew that melanomas can resist BRAF inhibitor drugs by activating a particular cancer pathway (a group of proteins in a cell that work together to control cell multiplication, which can lead to tumor growth)—but new research shows that this resistance can also be caused by activating a second cancer pathway. The first pathway is called MAPK and the second is called PI3K-PTEN-AKT. The researchers studied 100 melanomas that resisted the BRAF inhibitors vemurafenib or dabrafenib, and found that 70% had mutations in the first pathway, while 22% had mutations in the second pathway. Moreover, mutations in both pathways could occur in the same tumor, suggesting that thwarting resistance to BRAF inhibitors may require targeting both pathways with a combination treatment.


Resistance to BRAF Inhibitors Is More Complicated Than Thought

Two new studies show that several different genetic mutations can make melanoma tumors resist drugs known as BRAF inhibitors, complicating treatment. These mutations are in genes that are part of the ‘MAPK pathway.’ The first study was on BRAF-inhibitor resistant melanomas from 45 people. In about half of the tumors, one of a set of three genes (MEK1, MEK2, MITF) was abnormal, and in three of the tumors more than one was abnormal.

The second study compared melanomas before and after resistance to combination treatment with both BRAF and MEK inhibitors. Tumors from three of the five people in the study developed genetic abnormalities that were not seen before treatment. On a positive note, when cells from resistant melanomas with both BRAF and MEK mutations were grown in the laboratory, they responded to a drug that inhibits a related protein called ERK.

The mutations in this study were all found in genes that code for proteins in the MAPK pathway, a particular group of proteins in a cell that work together to control cell multiplication that can lead to tumor growth. Knowing exactly which mutations a melanoma has will help doctors target it with the right combination of treatments.


Combination Treatment Extends Life in People with Melanoma

Two targeted treatments that are U.S. Food and Drug Administration (FDA)-approved for melanoma may be even more effective together. The drugs are dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor. In a phase II clinical trial with 160 people, the median survival was nearly 2 years with the combination treatment compared to 20 months with dabrafenib alone. These findings were presented at the 10th International Congress of the Society for Melanoma Research in Philadelphia, Pennsylvania. Now, the dabrafenib/trametinib combo has advanced to phase III trials.


New Test May Reveal When Melanomas Resist Targeted Therapies

Melanomas with BRAF mutations often become drug-resistant, but now researchers think they know how to tell who will benefit from continued treatments. The researchers studied BRAF-mutant melanomas in nine people before and after targeted treatment, and found that tumors were less likely to grow when a protein called S6 was not activated. Next, the researchers developed a way to monitor S6 — and so tumor response —in treated melanomas in real-time. Their method entails fine-needle aspiration, which is far less invasive than conventional biopsies and could potentially replace the serial biopsies currently done to test for tumor resistance.


New Gene Linked to Melanoma in Mice

A new study shows that a gene involved in pancreatic cancer may also play a role in melanoma. The researchers found that when mice lack a gene called PDK1, their melanomas are smaller and less likely to spread. These mice also live longer. Likewise, when mice that have this gene are treated with a PDK1 inhibitor, melanomas are slower to form and hardly ever spread. If this gene is also linked to melanoma in people, it could provide a new target for treating this cancer.


FDA Asked to Approve New Combination Treatment for Melanoma

Two new drugs that target melanomas were approved by the US Food and Drug Administration in May, and the drug developer has already filed for approval to use them in combination. The drugs are dabrafenib (Tafinlar), a BRAF inhibitor, and trametinib (Mekinist), a MEK inhibitor, and both are made by GlaxoSmithKline. The combination treatment request is based on promising results of a Phase I/II trial, which showed that the two drugs work better together than dabrafenib does alone. Results of a Phase III trial of the combination therapy are expected later this year.