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Scientists Find New Way to Combat Drug Resistance in Skin Cancer

Scientists Find New Way to Combat Drug Resistance in Skin Cancer | Melanoma Dispatch | Scoop.it

"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.

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Medical Xpress  |  May 22, 2014

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DNA Shed by Tumors Shows Promise for Non-Invasive Screening and Prognosis

DNA Shed by Tumors Shows Promise for Non-Invasive Screening and Prognosis | Melanoma Dispatch | Scoop.it

"Certain fragments of DNA shed by tumors into the bloodstream can potentially be used to non-invasively screen for early-stage cancers, monitor responses to treatment and help explain why some cancers are resistant to therapies, according to results of an international study led by Johns Hopkins Kimmel Cancer Center investigators.


"Analyzing blood samples from 640 patients with various cancers, the researchers used digital polymerase chain reaction-based technology (a sophisticated method of multiplying and measuring the number DNA molecules) to evaluate how well the DNA fragments predicted the presence of tumors in the patients."

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Medical Xpress  |  Mar 6, 2014

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Medical Xpress  |  Mar 6, 2014

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Medical Xpress  |  Mar 6, 2014

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Blocking Autophagy with Malaria Drug May Help Overcome Resistance to Melanoma BRAF Drugs

Blocking Autophagy with Malaria Drug May Help Overcome Resistance to Melanoma BRAF Drugs | Melanoma Dispatch | Scoop.it

"Half of melanoma patients with the BRAF mutation have a positive response to treatment with BRAF inhibitors, but nearly all of those patients develop resistance to the drugs and experience disease progression.


"Now, a new preclinical study published online ahead of print in the Journal of Clinical Investigation from Penn Medicine researchers found that in many cases the root of the resistance may lie in a never-before-seen autophagy mechanism induced by the BRAF inhibitors vermurafenib and dabrafenib. Autophagy is a process by which cancer cells recycle essential building blocks to fuel further growth. Block this pathway with the antimalarial drug hydroxycholoroquine [sic] (HCQ), the authors found, and the BRAF inhibitors will be able to do their job better...


"Based on these promising preclinical results, Dr. Amaravadi and his team have already launched a clinical trial for patients with advanced BRAF mutant melanoma to see how well-tolerated HCQ is with the BRAF inhibitor vemurafenib. 'So far,' he said, 'we are seeing a benefit to patients and low toxicity.' "

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Medical Xpress  |  Feb 24, 2014

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New Drug May Overcome Cancer Treatment Resistance

An experimental drug could keep melanomas and breast cancer from resisting targeted therapies, according to findings reported at the 2013 International Conference on Molecular Targets and Cancer Therapeutics. Called LEE011, the new drug inhibits proteins called cyclin-dependent kinases (CDKs), which make cells divide. The targeted CDKs are abnormally active in many cancers, including melanomas with BRAF mutations and breast cancers with PIK3CA mutations. The researchers found that LEE011 keeps cultured tumor cells from dividing and that combining the drug with targeted treatments prevents resistance in melanomas and breast cancer in mice. Now, these combination treatments are being tested in several phase I clinical trials on a variety of cancers in adults, as well as in children.

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American Association for Cancer Research │Oct 20, 2013

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Conference Abstract - MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients With Acquired Resistance to Combined RAF/MEK Inhibition

Conference Abstract - MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients With Acquired Resistance to Combined RAF/MEK Inhibition | Melanoma Dispatch | Scoop.it

"Treatment of BRAF-mutant melanoma with combined dabrafenib and trametinib, which target RAF and the downstream MAP–ERK kinase (MEK)1 and MEK2 kinases, respectively, improves progression-free survival and response rates compared with dabrafenib monotherapy. Mechanisms of clinical resistance to combined RAF/MEK inhibition are unknown. This study represents an initial clinical genomic study of acquired resistance to combined RAF/MEK inhibition in BRAF-mutant melanoma, using WES and RNA-seq. The presence of diverse resistance mechanisms suggests that serial biopsies and genomic/molecular profiling at the time of resistance may ultimately improve the care of patients with resistant BRAF-mutant melanoma by specifying tailored targeted combinations to overcome specific resistance mechanisms."


Editor's note: We previously covered the benefits of a dabrafenib/trametinib combo for advanced-stage melanoma. However, some patients' tumors become resistant to this drug combination and new treatment routes need to be considered. This study is exploring how molecular testing of specific genetic mutations in patients' tumors might be used to help guide treatment decisions after they become resistant to the dabrafenib/trametinib combo.

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MDLinx  |  Apr 8, 2014

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Enhancement of Chemotherapy by Prevention of Tumor Cell Repair

"The body naturally tries to repair lesions in the DNA of tumor cells, and thus reduces the efficacy of chemotherapy. Blocking the mechanisms for DNA repair would help to potentiate chemotherapy by reducing the resistance of cells to treatment. A team of scientists has discovered a new drug that inhibits repair: spironolactone, which seems likely to be used in the very short term as an adjuvant to chemotherapy."

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ScienceDaily  |  Feb 20, 2014

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ScienceDaily  |  Feb 20, 2014

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ScienceDaily  |  Feb 20, 2014

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New Melanoma Combo Treatment Is Promising in Early Trial

Because melanomas can quickly resist BRAF inhibitor drugs alone or in combination with MEK inhibitors, researchers are testing a new combination treatment: the BRAF inhibitor vemurafenib and PX-866, which inhibits a cancer pathway called PI3K. In a phase I/II clinical trial of 19 people with melanomas that have BRAF mutations, the vemurafenib/PX-866 combination shrank tumors in 10 of them. These findings were presented at the 10th International Congress of the Society for Melanoma Research in Philadelphia. However, while results so far are encouraging, it will take larger trials to see if this new combo treatment really overcomes drug resistance in melanomas. This ongoing trial is still accepting new participants.

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Cancer Network  |  Nov 25, 2013

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