Question

explain 1 or 2 molecular details in how epigenetics may allow melanoma cells to outsmart BRAF inhibitors

**This is for a genetics course

Seope: This science commentary claims that epigeneties plays a role in cancer cells becoming therapy-resistant. The language used is generalized for the non-scientist and does not include any molecular details, such as methylation of a specific nucleotide in an allele or modification of a specific histone tail amino acid. Your task (individually or in a group of your BIOL 304 classmates of any size): 1. Read this entire commentary. 2. Perform a literature search for the research paper on which the claim that epigenetics lets cancer cells become therapy-resistant is based. (Hint: I think the research occurred in the lab of this commentary author). 3. In some combination of words and drawing, explain one Keep response as succinct as possible. or two molecular details in how epigenetics, not mutation, may allow melanoma cells to outsmart BRAF inhibitors. a. i. Submission should not take up more than one page. ii. No more than 300 words of text. ii. Well-labeled cartoon-like drawings are encouraged. Plagiarism of any part of the research article will result in an immediate zero for this assignment for all individuals participating in the offending submission. b. How Cancer Can Become Therapy- Resistant Epigeneties may play a role READ THIS NEXT of advances in drug design and precision medicine, researchers have been able to target certain molecules disease and to develop specific therapies to undo their damages. Today, with molecular insights to offer hope after a life-changing cancer Because within a cell at the root of a particular precision targeting combines therapy decisions diagnosis. But there's a dark side to cancer-killing drugs designed to match distinct cancer mutations like a key into a lock. Some cancers that initially respond to targeted chemotherapy become treatment-resistant -and the drug itself may not be the culprit. New research helps explain how therapy-resistant cancers arise, findings wit future of cancer therapy. It shows how hidden, subtle layers of regulation-epigenet genes to produce drug-resistant surviving cells. cs-control the activity of of cancer across many tumor types is that patients fall back into the state of illness after elucidating the network of changes within cells as a way to identilt apparent recovery. My cancer systems biology team at the University of California, Merced, is tackling diagoss and treatment of therapy-resistant cancers by new drug targets and circumvent cancer resistance A HIDDEN LAYER OF REGULATION It is well established that cancer is a disease of our genes. However, resistance to therapym mutations that usually alter the function of genes. It may not be new mutations that are ight go beyond cancer A can stay the same, but cancer cells adapt to therapy and outsmart the drugs by switching their gence activity While such adaptations do not affect the DNA itself, a hidden layer of regulation controlling the activity of genes -epigenetic signals -is responsible for whether cancer cells survive or not, despite the drug a patient is taking. By targeting this hid den program, one can overcome deadly cancer resistance. CANCER SYSTEMS BIOLOGY REVEAL NEW TARGETS AND CHALLENGES To understand how cancer becomes treatment-resi stant, my research team at the Systems Biology and Cancer Lab at UC Merced compared genetic and metabolic pathways in treatment-responsive and treatment- resistant melanomas. Melanoma is a cancer that originates in melanocytes, the cells that produce the skin-color pigment melanin. Though not the most common form of skin cancer, melanoma is the most aggressive. And if it's not caught and treated early, it's also among the deadliest. ACQUIRED RESISTANCE BEYOND MUTATIONS Cancer can be triggered by different causes. Melanoma is usually induced by the sun, by dangerous ultraviolet V damage leaves a unique mutational footprint behind and as a result unstoppable cell proliferation is induced UV damage gives rise to point mutations-changes in a single letter of the 3 billion letter human genome. These mutations can interfere with signals that tell cells when to grow and divide and when to stop. Mutations in protein called BRAF, a major signaling regulator, cause growth signals to be stuck in the"on" position and drive cancer development. Though scientists have managed to come up with drugs that target and turn off aberrant BRAF signaling, cancer cells are clever. They learn to adapt to very positively at first. However, unfortunately many ultimately develop resistance and metastases. Though chemotherapy might kill most of the cancer, tiny populations of drug-resistant cancer cells survive and propagate. Unlike the more familiar case of antibiotic-resistant bacteria, where genetic rise to resistance, many adaptations in treatment-resistant cancers aren't the result of mutation. these BRAF-inhibitors. Today, many patients respond to cancer treatment REWIRING OF GENE EXPRESSION TO BYPASS DRUG RESISTANCE Instead, cancer cells adapt to therapy and outsmart the drugs. Melanoma is able to circumvent BRAF inhibi not by changing the genes themselves, but by changing gene activity. Some of the genes with reduced activit were supposed to be in close communication with BRAF and safeguarding its targets, the mutated protein that gave rise to the cancer and the main target of chemotherapy. If essential off switches are lost, they can trigger th tumor cells to divide despite presence of inhibitors. The resistant cells managed to evolve in a way to bypass the signaling blockade or come up with a new way to maintain proliferation. Genes with increased activity are in metabolic pathways that allowed cancer cells to bypass BRAF altogether and continue to grow and divide. Cancer cells had essentially figured out how to survive by rewiring their metabolism in response to chemotherapy. The research explains how tumors evolve and cause cancer resistance to drugs designed to match the patient's unique genomic makeup. Daunting as this may sound, it actually offers hope to scientists and clinicians who want to treat chemo-resistant cancers. The research brought forward valuable tools that will enable us to catch new forms of disease resistance before treatment regiments enter clinical trials. This article was originally published on The Conversation

Answer 1

Epigenetics brings changes in the gene expression without changing the DNA sequence.

Many braf inhibitors are synthesized , which can block the MEK pathway.

Epigenetic modifications like methylation and action of histone deacetylase binds to the DNA itself and stop the gene expression. This method does not allow the gene expression and there is no other alternative pathway occuring unlike that of the inhibition drugs. Inhibitors may also have some side effects.