Research by Umass Chan Medical School Scientists Sharon Cantor, Ph.D., And Jenna M. WH.D.., poses a new explanation for how Cancer-Fighting Drugs Attack and Destroy Tumor Cells.

Their work, Published in Nature cancerIllustrates how a small dna nick-a break in one strand of the dna –Can expand into a large single-stranded DNA Gap, Killing BRCA MUTANT CANCER CHELLS, Including Drug -resest Breast Breast Breast Cells. These Findings Identify a novel vulnerability that may be a potential target for new the therapeutics.

Mutations in BRCA1 and Brca2 – Tumor Supppressor Genes That Play a Crucial Role in DNA Repair – Substantily Increase the Likelihood of Cancer. These cancers are, however, quite sensitive to anticancer drugs When successful, these cancer treatments cause enough DNA Damage to Trigger Cancer Cell Death.

However, the array of different damages potentially induced by these drugs makes it diges Additional, Parpi Resistance does Occur, Complicating Treatment and Leading to Recurrent Cancer.

“The Conventional Thinking Has Been that Single-Stranded DNA Breaks from Parpi Ultimetely Generated DNA Double-Strand Breaks, and that was what was welling the brca mutant cancer cells,” Cantor, The Gladys Smith Martin Chair in Oncology and Professor of Molecular, Cell and Cancer Biology.

“Yet, there wasn’t much in the literature that experienceally confirmed this belief. DNA. “

Using Crispr Technology, Cantor and Dr. Whalen, a postdoctoral researchr in the cantor lab, introduced small, single-strand breaks into several breast cancer cell lines, thought as that with the brca1 and brca2 mute, as w well. Brca-deficient cells. They found that cells with Brca1 or Brca2 deficiency was uniquely sensitive to nicks.

They also found that breast cancer cells that lose components of the complex that protects dna from unnecessary dna end cuts become resistant to chemotherapy drugs inhibit

However, Restoring Double-Strand DNA REPAR Functions in Breast Cancer Cells Did Not Save the Cells from Dying, Thus Demonstrating that these Repair Functions are not Critical For Cancet Cancer Cell Survival. INTEAD, the cells become even more sensitive to Single Strand Nicks, Who then Accumulate and Form Large Gaps.

“Our Findings Reveal That It is the Resection of a Nick INTO A Single-Stranded DNA Gap That Drives This Cellular Lethality,” said wheeln. “This highlights a distinct mechanism of cytotoxicity, where excessive research, raather than failed DNA repair by homologous recombination, underpins the vulnerability of ar Nick-Induced Damage. “

The findings sugges that parpi may also work by generating nicks in Brca1 and brca2 cancer cells, exploiting their inability to effectively process these lesions. For cancers that have developed parpi-resistance, nick-inducing therapies provide a promising mechanism to bypass resistance and selectively target responsibility-dependent vulnerabilityes.

“Importantly, our Findings Suggesst a Path Forward for Treating Parpi-resistant cells that Regained Homologous Recombination Repair: To Kill these cells, nicks clock be inuduced free Ionizing Radiation, “Said Cantor. “By targeting nicks in this way, therapies should effectively exploit the personality vulnerabilityes of these resistant cancer cells.”