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Mashup Score: 46Sotorasib Is a Pan-RASG12C Inhibitor Capable of Driving Clinical Response in NRASG12C Cancers - 20 day(s) ago
AbstractKRASG12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRASG12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRASG12C tumors. Because amino acid sequences of the three main RAS isoforms—KRAS, NRAS, and HRAS—are highly similar, we hypothesized that some KRASG12C inhibitors might also target NRASG12C and/or HRASG12C, which are less common but critical oncogenic driver mutations in some tumors. Although some inhibitors, like adagrasib, were highly selective for KRASG12C, others also potently inhibited NRASG12C and/or HRASG12C. Notably, sotorasib was five-fold more potent against NRASG12C compared with KRASG12C or HRASG12C. Structural and reciprocal mutagenesis studies suggested that differences in isoform-specific binding are mediated by a single amino acid: Histidine-95 in KRAS (Leucine-95 in NRAS). A patient with NRASG12C colorectal cancer treated with sotorasib and the anti-EGFR antibody panitumumab achieved
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 46Sotorasib Is a Pan-RASG12C Inhibitor Capable of Driving Clinical Response in NRASG12C Cancers - 20 day(s) ago
AbstractKRASG12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRASG12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRASG12C tumors. Because amino acid sequences of the three main RAS isoforms—KRAS, NRAS, and HRAS—are highly similar, we hypothesized that some KRASG12C inhibitors might also target NRASG12C and/or HRASG12C, which are less common but critical oncogenic driver mutations in some tumors. Although some inhibitors, like adagrasib, were highly selective for KRASG12C, others also potently inhibited NRASG12C and/or HRASG12C. Notably, sotorasib was five-fold more potent against NRASG12C compared with KRASG12C or HRASG12C. Structural and reciprocal mutagenesis studies suggested that differences in isoform-specific binding are mediated by a single amino acid: Histidine-95 in KRAS (Leucine-95 in NRAS). A patient with NRASG12C colorectal cancer treated with sotorasib and the anti-EGFR antibody panitumumab achieved
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 3Segmenting the Utility of ADCs in NSCLC: How These Agents Are Affecting Second-Line Standards - 20 day(s) ago
Keeping investigators on the edge of their seats, new data from clinical trials evaluating ADCs continue to impress.
Source: www.onclive.comCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 0
Several patients with TP53 Y220C–mutated ovarian cancer experience tumor shrinkage following treatment with rezatapopt in the phase 1/2 PYNNACLE study.
Source: www.cancernetwork.comCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 46Sotorasib Is a Pan-RASG12C Inhibitor Capable of Driving Clinical Response in NRASG12C Cancers - 20 day(s) ago
AbstractKRASG12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRASG12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRASG12C tumors. Because amino acid sequences of the three main RAS isoforms—KRAS, NRAS, and HRAS—are highly similar, we hypothesized that some KRASG12C inhibitors might also target NRASG12C and/or HRASG12C, which are less common but critical oncogenic driver mutations in some tumors. Although some inhibitors, like adagrasib, were highly selective for KRASG12C, others also potently inhibited NRASG12C and/or HRASG12C. Notably, sotorasib was five-fold more potent against NRASG12C compared with KRASG12C or HRASG12C. Structural and reciprocal mutagenesis studies suggested that differences in isoform-specific binding are mediated by a single amino acid: Histidine-95 in KRAS (Leucine-95 in NRAS). A patient with NRASG12C colorectal cancer treated with sotorasib and the anti-EGFR antibody panitumumab achieved
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 6
Adagrasib improved progression-free survival and objective response rates vs docetaxel in pretreated KRAS G12C–mutant non–small cell lung cancer.
Source: www.onclive.comCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 1Perioperative Pembrolizumab Wins Approval in Europe for Resectable NSCLC at High Risk of Recurrence - 22 day(s) ago
The European Commission has approved neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab, for high-risk, resectable NSCLC.
Source: www.onclive.comCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 3Segmenting the Utility of ADCs in NSCLC: How These Agents Are Affecting Second-Line Standards - 23 day(s) ago
Keeping investigators on the edge of their seats, new data from clinical trials evaluating ADCs continue to impress.
Source: www.onclive.comCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 6
Adagrasib improved progression-free survival and objective response rates vs docetaxel in pretreated KRAS G12C–mutant non–small cell lung cancer.
Source: www.onclive.comCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 8I Am RETpositive: Who We Are - 24 day(s) ago
“There’s a lot of joy in the life you are given after a cancer diagnosis. It just may look a little different than the life you were expecting.” RETpositive …
Source: www.youtube.comCategories: General Medicine News, Onc News and JournalsTweet
Sotorasib is a Pan-RASG12C-, with activity in NRASG12C+ cancers @CD_AACR: - sotorasib 5x ⬆️potent against NRASG12C vs KRASG12C or HRASG12C (activity in all) - pt w NRASG12C+ CRC had prolonged response to soto+panitumumab @OncoAlert #LCSM https://t.co/bowOYELJVJ