Scientists Find New Way to Combat Drug Resistance in Skin Cancer

“Rapid resistance to vemurafenib – a treatment for a type of advanced melanoma, the deadliest form of skin cancer – could be prevented by blocking a druggable family of proteins, according to research published in Nature Communications today.

“Scientists at the Cancer Research UK Manchester Institute, based at the University of Manchester, have revealed the MLK family of four enzymes ‘undoes’ the tumour-shrinking effects of vemurafenib.”

Editor’s note: This story describes a potential new way to treat melanoma that has become resistant to vemurafenib. While promising, the research is still in preliminary stages, so new treatments are not yet available for patients.


Thwarting Drug Resistance in Lung Cancer


If you’ve read up on lung cancer research in the last few years, you probably know that large strides have been made in targeted therapies for non-small cell lung cancer (NSCLC). Targeted therapies are drugs that identify and attack specific mutated proteins that are detected in tumors. Because noncancerous cells do not have these specific mutations, targeted therapies can make a beeline for cancer, while leaving healthy tissue unharmed. Continue reading…


Immunotherapy, BRAF Inhibitor Sequence Affected Outcomes in Metastatic Melanoma

“Prior treatment with immunotherapy did not limit response to BRAF inhibitors among patients with metastatic melanoma, according to results of a retrospective study.

“However, patients who underwent initial treatment with BRAF inhibitors and subsequently received immunotherapy with ipilimumab (Yervoy, Bristol-Myers Squibb) demonstrated poorer outcomes, results showed.

“Patients with BRAF-positive metastatic melanoma have several treatment options, including BRAF inhibitors vemurafenib (Zelboraf, Hoffmann-La Roche) and dabrafenib  (Taflinar, GlaxoSmithKline), the MEK inhibitor trametinib (Mekinist, GlaxoSmithKline), and the immunotherapy agents ipilimumab and interleukin-2. Yet, there are limited data with regard to optimal sequencing, according to researchers.”


‘Real World’ Safety Study of Vemurafenib in BRAF V600–Mutated Metastatic Melanoma Shows Similar Safety Profile as Pivotal Trials

“As reported in The Lancet Oncology by Larkin et al, interim results of a safety study designed to reflect the spectrum of patients encountered in routine practice suggest that vemurafenib (Zelboraf) has a safety profile in patients with BRAF V600–mutated metastatic melanoma similar to that observed in the more select patient population included in registration trials. The study included patients with limited treatment options and sizable proportions with brain metastases, elevated lactate dehydrogenase (LDH), poor performance status, and age ≥ 75 years.”

Editor’s Note: The important takeaway from this story is that the drug vemurafenib can be used safely and effectively in some melanoma patients with poor prognoses, who may not fit the profile of patients typically enrolled in clinical trials to test the drug. To learn more about clinical trials and “targeted therapies” like vemurafenib, visit our Melanoma Basics.


Extended Follow-up in BRIM-3 Shows Prolonged Survival With Vemurafenib in BRAF V600E/K Mutation–Positive Melanoma

In the BRIM-3 trial, vemurafenib (Zelboraf) was associated with improved progression-free and overall survival vs dacarbazine in patients with advanced BRAF V600 mutation–positive melanoma. In an extended follow-up reported in The Lancet Oncology, McArthur et al found that superior survival outcomes were maintained and were present in both theBRAF V600E and BRAF V600K mutation subgroups.”

Editor’s note: Read more about vemurafenib here: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a612009.html


Trial Supports Recent US FDA Approval of New Melanoma Combo Treatment

The US Food and Drug Administration just granted accelerated approval for a treatment that combines two drugs that target melanomas with BRAF mutations — but this was contingent on the results of an ongoing phase III clinical trial. The drugs are the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist). Now the latest results of the trial are in and they look good. This combination treatment is not approved elsewhere in the world, and the trial included 423 people from Australia, Europe, and North and South America. Final results are expected later this year and will be presented at a scientific meeting. In addition, another trial is comparing this combination treatment to the BRAF inhibitor vemurafenib (Zelboraf), which is also FDA-approved.


Melanoma: A 2013 ‘Progress Report’


The past year saw some remarkable advances in melanoma clinical research and treatment. This feature explores the most notable melanoma news of 2013: Continue reading…


Patient’s Perspective: Erin Youngerberg’s Take on Melanoma


Erin Youngerberg was diagnosed with melanoma in October, 2010, at age 32 years. Well-traveled and an avid photographer, she grew up in Minnesota, went to college and worked in Milwaukee, then made her way east, living in Ohio and North Carolina before ending up in Jersey City, just outside of New York City. After her diagnosis, she started a blog to keep folks back home updated. Called ‘Melanoma and the City,’ it tells the whole story: from appointments at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City to various city adventures; from treatment side effects to recipes for quinoa and tacos. Erin has also found herself dedicated to spreading the word about melanoma awareness. We asked her to take us through her melanoma story. Continue reading…


Therapeutic Destruction of Insulin Receptor Substrates for Cancer Treatment

“Insulin receptor substrates 1 and 2 (IRS1/2) mediate mitogenic and antiapoptotic signaling from insulin-like growth factor 1 receptor (IGF-IR), insulin receptor (IR), and other oncoproteins. IRS1 plays a central role in cancer cell proliferation, its expression is increased in many human malignancies, and its upregulation mediates resistance to anticancer drugs. IRS2 is associated with cancer cell motility and metastasis. Currently, there are no anticancer agents that target IRS1/2. We present new IGF-IR/IRS-targeted agents (NT compounds) that promote inhibitory Ser-phosphorylation and degradation of IRS1 and IRS2. Elimination of IRS1/2 results in long-term inhibition of IRS1/2-mediated signaling. The therapeutic significance of this inhibition in cancer cells was shown while unraveling a novel mechanism of resistance to B-RAFV600E/K inhibitors. We found that IRS1 is upregulated in PLX4032-resistant melanoma cells and in cell lines derived from patients whose tumors developed PLX4032 resistance. In both settings, NT compounds led to the elimination of IRS proteins and evoked cell death. Treatment with NT compounds in vivo significantly inhibited the growth of PLX4032-resistant tumors and displayed potent antitumor effects in ovarian and prostate cancers. Our findings offer preclinical proof-of-concept for IRS1/2 inhibitors as cancer therapeutics including PLX4032-resistant melanoma. By the elimination of IRS proteins, such agents should prevent acquisition of resistance to mutated-B-RAF inhibitors and possibly restore drug sensitivity in resistant tumors.”