Targeting Mutation May Offer Way of Treating Triple-Negative Breast Cancer

Targeting Mutation May Offer Way of Treating Triple-Negative Breast Cancer

Researchers in Ireland may have found a promising treatment for patients with triple-negative breast cancer, the most aggressive form of breast cancer.

Their study, “Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer?,” published in the International Journal of Cancer, shows that a drug which targets the p53 mutated protein can largely inhibit triple-negative breast cancer cell proliferation and migration, while also promoting programmed cell death.

Currently, the most successful breast cancer treatments target one of three classes of hormone receptors found at the surface of cancer cells — estrogen receptors, progesterone receptors, and HER2 receptors. However, one in every six breast cancer patients do not express any of these receptors in their tumors,making their treatment difficult.

“At the moment the only form of drug treatment available to patients with triple negative breast cancer is chemotherapy,” Naoise Synnott, a PhD student at the Breast-Predict research group at University College Dublin, and the study’s lead author, said in a press release. “While this will work well for some patients, others may find that their cancer cells don’t respond as well as might be hoped to chemo, leading patients suffering the side effects of this treatment without any of the desired outcomes.”

Nearly 80 percent of triple-negative breast cancers carry mutations in the p53 protein, however.

p53, one of the most studied genes in cancer, is a tumor suppressor gene that prevents cancer from arising in a number of ways. These include blocking cell proliferation when DNA damage is found, activating DNA damage repair mechanisms, and initiating programmed cell death if the damage is irreparable. But when the p53 gene is mutated, tumor suppression is severely compromised.

Not surprisingly, most tumors eventually acquire mutations in this gene, as a means of escaping the regulatory powers exerted by p53.

But studies have shown that restoring normal p53 function holds some promise in such tumors. APR-246, in particular, has the ability to bind the mutated p53 protein and induce conformational changes that restore its intended chores, leading to tumor cell cycle arrest and apoptosis.

Using a panel of 18 breast cancer cell lines, the researchers demonstrated that APR-246, an investigational compound, may also work in triple-negative breast cancer cells, inhibiting tumor cell proliferation and migration, and inducing apoptosis in a p53 mutant-dependent manner — the more mutated p53 a cell line had, the better the treatment worked.

“Based on our data, we conclude that targeting mutant p53 with [APR-246] is a potential new approach for treating p53-mutated breast cancer, including the subgroup with triple-negative (TN) disease,” the researchers wrote.

5 comments

  1. Wanda Northam, MD says:

    Nice and all but if we don’t get past the mouse model immediately tens of thousands of women continue to die of TNBC every year. TNBC is not your run of the mill breast cancer. Essentially 50/50 odds of survival with TNBC! Urgency is needed for TNBC research. Way past time for mouse models. This should have been done 10-12 years ago when TNBC identified as one of the primary reasons some 15-20% of people with breast cancer died with the typical blanket treatment of surgery, Chemo and radiation. Well, we continue to die, and I’m not talking about years down the road. It is typically within 3-5 years of original diagnosis if it becomes metaststic. Time to work on curing HUMANS! Redouble your efforts! Our futures depend on it.

    • Tim Bossie says:

      We couldn’t agree with you more Wanda. Let us hope that we can advance to human trials and begin to unlock the TNBC mystery.

  2. Anisa M Malik says:

    Dr.Martins. please do everything you can to move trials to patients who have exhausted all other treatment options. These people have nothing to lose and everything to gain if you can trial this drug if they are willing to give it a go. It’s like Dr. Northampton said, people are dying. God bless you for your research and I hope He gives you success.

  3. LuAnn says:

    I am an early stage TNBC patient. My cancer was found on a mammogram on 12/27. Ultrasound and biopsy was performed and found TNBC with a proliferation rate of 95%; grade 3/3. In 3 weeks my cancer grew from 5 mm to 10 mm. I know that I am blessed to have found it so early. Lumpectomy was done with clear margins and no lymph node involvement. Being treated with dose dense A/C (4 cycles) and now 12 weeks of Taxol. Then 6 weeks of radiation. No BRCA mutations found – but have NBN variant gene. Should I be doing more treatments or more testing of my tumor. I am a retired nurse and am fully aware of me blessed to have found this so early and know I may not be as blessed the next time. What more should I do? I maintain my weight, exercise 1-2 hours/day, eat healthy (except loved chocolate – but no more!). Please direct me. I feel that when treatment is over……wait and see?

  4. Shelley Ortiz says:

    I was just diagnosed with Cowdens syndrome. My gene mutation,pten doesn’t work at all. Would this study help me?

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