{"id":411556,"date":"2026-04-22T10:13:12","date_gmt":"2026-04-22T10:13:12","guid":{"rendered":"https:\/\/www.newsbeep.com\/ie\/411556\/"},"modified":"2026-04-22T10:13:12","modified_gmt":"2026-04-22T10:13:12","slug":"study-holds-promise-for-targeting-elusive-p53-gene-mutation","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ie\/411556\/","title":{"rendered":"Study Holds Promise for Targeting Elusive P53 Gene Mutation"},"content":{"rendered":"

Earlier this month, researchers shared that they may have discovered a way to target a key driver of many cancerous masses. The outcomes of this proof of concept study were published in the New England Journal of Medicine.<\/a><\/p>\n

Advertisement<\/p>\n

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy<\/a><\/p>\n

Background<\/p>\n

The p53 protein is mutated in roughly 50% of cancerous growths \u2013 including 90% of ovarian cancers \u2013 but it has been an undruggable target until now due in part to its genetic diversity.<\/p>\n

Targeting the p53 mutation has long confounded researchers seeking a more effective way to treat solid tumors. \u201cWe knew p53 existed and impacted cancer but didn\u2019t have a way to do anything about it,\u201d says study co-author Dale Shepard, MD, PhD<\/a>, a medical oncologist, member of the Novel Therapeutics Program and Director of Global Oncology Partnerships at Cleveland Clinic Cancer Institute.<\/p>\n

Recently, a group of researchers found a way around this problem. They discovered that the small molecule drug rezatapopt had the potential to bind to Y220C, which is a targetable section of the p53 protein. The therapy reactivates p53 and restores its functionality.<\/p>\n

Study design<\/p>\n

In a phase 1 study, researchers investigated the use of rezatapopt for 21-day treatment cycles in patients with locally advanced or metastatic solid tumors with the p53 Y220C mutation. The goal was to identify the maximum tolerated dose as well as the recommended dose for a phase 2 trial. Primary endpoints included dose-limiting adverse events while secondary endpoints included efficacy and identification of pharmacokinetic characteristics.<\/p>\n

Seventy-seven patients enrolled in the trial and received gradually increasing doses starting at 150 mg and titrating up to 1,500 mg twice a day. Patients had an average of four previous lines of therapy.<\/p>\n

Study outcomes<\/p>\n

Initial study results demonstrated antitumor activity across many types of advanced solid tumors, including breast, ovarian, head and neck, endometrial and pancreatic cancer. Overall, 20% of patients had a partial or complete response, while 30% of those patients with the KRAS wild-type tumor who received a minimum dose of 1,150 mg experienced a partial or complete response.<\/p>\n

\u201cThe results are early but promising given that these were patients who had been heavily pretreated,\u201d says Dr. Shepard. \u201cThis data shows the potential for treating cancers that we were previously unable to do.\u201d<\/p>\n

The oral therapy was well tolerated. Of the 77 patients in the study, 38% experienced grade 1 or 2 side effects. The most common side effects were nausea (58%), vomiting (44%), elevated blood creatinine level (39%), fatigue (39%) and anemia (36%). Most GI side effects resolved with symptom treatment and reduced when the medication was taken with food. Two patients stopped treatment due to adverse events.<\/p>\n

What\u2019s next<\/p>\n

Based on the phase 1 study outcomes, the trial sponsor has opened a phase 2 study focused on using rezatapopt specifically to treat ovarian cancer. Cleveland Clinic Cancer Institute is participating in the phase 2 trial, which is enrolling patients with ovarian cancer who have the Y220C mutation in P53.<\/p>\n

Depending on the results of that study, the medication may be tested across additional types of solid tumors in the future.<\/p>\n","protected":false},"excerpt":{"rendered":"Earlier this month, researchers shared that they may have discovered a way to target a key driver of…\n","protected":false},"author":2,"featured_media":411557,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[103,61,60],"class_list":{"0":"post-411556","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-health","9":"tag-ie","10":"tag-ireland"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/411556","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=411556"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/411556\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/411557"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=411556"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=411556"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=411556"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}