\u4f20\u7edfAR\u6291\u5236\u5242\u7684\u5de5\u4f5c\u65b9\u5f0f\u662f\u201c\u5835\u201d\u2014\u2014\u5360\u636eAR\u7684\u914d\u4f53\u7ed3\u5408\u53e3\u888b\uff0c\u963b\u6b62\u96c4\u6fc0\u7d20\u6fc0\u6d3b\u53d7\u4f53\u3002\u4f46LBD\u7a81\u53d8\u6216AR-V7\u526a\u63a5\u53d8\u4f53\u7684\u51fa\u73b0\uff0c\u4f7f\u8fd9\u6761\u8def\u5f84\u9891\u7e41\u5931\u6548\u3002PROTAC\u6280\u672f\u7684\u601d\u8def\u5b8c\u5168\u4e0d\u540c\uff1a\u4e0d\u5835\uff0c\u800c\u662f\u76f4\u63a5\u964d\u89e3AR\u86cb\u767d\u3002<\/p>\n\n\n\n
\u9f50\u9c81\u5236\u836f\u7684QLH12016\u57282025\u5e74ESMO\u5927\u4f1a\u4e0a\u516c\u5e03\u4e86I\u671f\u7814\u7a76\u6570\u636e\u3002\u622a\u81f32025\u5e747\u67081\u65e5\uff0c44\u4f8b\u60a3\u8005\u63a5\u53d7QLH12016\u6cbb\u7597\uff08100-1200mg\u6bcf\u65e5\u4e00\u6b21\uff09\uff0c72.7%\u7684\u60a3\u8005\u4e3aLBD\u91ce\u751f\u578b\uff0c27.3%\u5b58\u5728LBD\u7a81\u53d8\uff08\u542bL702H\u7a81\u53d8\uff09\u3002\u672a\u89c2\u5bdf\u5230\u5242\u91cf\u9650\u5236\u6027\u6bd2\u6027\uff0c\u672a\u8fbe\u5230\u6700\u5927\u8010\u53d7\u5242\u91cf<\/a> [2,3]<\/sup>\u3002<\/p>\n\n\n\n \u7597\u6548\u65b9\u9762\uff0c14\u4f8b\u60a3\u8005\u5b9e\u73b0PSA30\u5e94\u7b54\uff0c9\u4f8b\u5b9e\u73b0PSA50\u5e94\u7b54\uff0c\u5404\u5242\u91cf\u7ec4\u5747\u6709PSA\u5e94\u7b54\u3002\u572817\u4f8b\u6709\u57fa\u7ebf\u9776\u75c5\u7076\u7684\u60a3\u8005\u4e2d\uff0c4\u4f8b\uff0823.5%\uff09\u8fbe\u5230\u90e8\u5206\u7f13\u89e3\uff0c\u5ba2\u89c2\u7f13\u89e3\u738723.5%\uff0c\u75be\u75c5\u63a7\u5236\u738770.6%\u3002\u5168\u4eba\u7fa4\u4e2d\u4f4drPFS\u4e3a7.4\u4e2a\u6708\uff0c600mg\u5242\u91cf\u7ec4\u4e2d\u4f4drPFS\u4e3a9.2\u4e2a\u6708\u3002\u4e9a\u7ec4\u5206\u6790\u663e\u793a\uff0cLBD\u7a81\u53d8\u60a3\u8005\uff08n=12\uff09\u4e2d\u4f4drPFS\u4e3a5.3\u4e2a\u6708\uff0cLBD\u91ce\u751f\u578b\u60a3\u8005\uff08n=32\uff09\u4e2d\u4f4drPFS\u4e3a9.2\u4e2a\u6708\u3002<\/p>\n\n\n\n <\/a>HP518<\/a>\u662f\u4e2d\u56fd\u9996\u6b3e\u8fdb\u5165\u4e34\u5e8a\u9636\u6bb5\u7684\u53e3\u670dAR PROTAC\u3002\u5176I\u671f\u7814\u7a76\u5165\u7ec4mCRPC\u60a3\u8005\uff0c3\u4f8b\u60a3\u8005\u5b9e\u73b0PSA50\u5e94\u7b54\uff0c2\u4f8b\u60a3\u8005\u786e\u8ba4\u90e8\u5206\u7f13\u89e3\uff0c\u7597\u6548\u5206\u522b\u6301\u7eed36\u5468\u548c60\u5468\uff0c\u5176\u4e2d1\u4f8b\u60a3\u8005\u809d\u810f\u75c5\u7076\u7f29\u5c0f80%[4]<\/sup>\u3002\u5728\u809d\u8f6c\u79fb\u88ab\u89c6\u4e3a\u201c\u9884\u540e\u6700\u5dee\u3001\u73b0\u6709\u6cbb\u7597\u6700\u4e0d\u654f\u611f\u201d\u7684\u80cc\u666f\u4e0b\uff0cHP518\u80fd\u8ba9\u809d\u8f6c\u79fb\u75c5\u7076\u51fa\u73b0\u663e\u8457\u7684\u7f29\u5c0f\uff0c\u4e14\u7ef4\u6301\u8d85\u8fc7\u4e00\u5e74\uff0c\u63d0\u793a\u5176\u5728\u809d\u8f6c\u79fb\u8fd9\u4e00\u96be\u6cbb\u4e9a\u7fa4\u4e2d\u5177\u6709\u6f5c\u5728\u6d3b\u6027\u3002\u3002<\/p>\n\n\n\n Monte Rosa\u7684MRT-2359\u662f\u4e00\u79cd\u53e3\u670dGSPT1\u5206\u5b50\u80f6\u964d\u89e3\u5242\u30022026\u5e74ASCO GU\u4e0a\u66f4\u65b0\u7684\u6570\u636e\u663e\u793a\uff0c\u57285\u4f8b\u643a\u5e26AR\u7a81\u53d8\u7684mCRPC\u60a3\u8005\u4e2d\uff0c5\u4f8b\uff08100%\uff09\u5b9e\u73b0PSA\u5e94\u7b54\uff0c\u5305\u62ec2\u4f8bPSA90\u548c3\u4f8bPSA50\uff0c\u75be\u75c5\u63a7\u5236\u7387100%\u3002\u6240\u670915\u4f8b\u53ef\u8bc4\u4f30\u60a3\u8005\u4e2d\uff0cRECIST\u75be\u75c5\u63a7\u5236\u7387\u4e3a67%\uff0c10\u4f8b\u60a3\u8005\u9776\u75c5\u7076\u7f29\u5c0f[5]<\/sup>\u3002\u57fa\u4e8e\u6b64\uff0c\u9488\u5bf9AR\u7a81\u53d8\u60a3\u8005\u7684II\u671f\u7814\u7a76\uff08MODeFIRe-1\uff0cNCT07745361\uff09\u5df2\u4e8e2026\u5e748\u670824\u65e5\u5b8c\u6210\u9996\u4f8b\u60a3\u8005\u7ed9\u836f\uff0c\u8ba1\u5212\u5165\u7ec425\u4f8b\uff0c\u4e3b\u8981\u7ec8\u70b9\u4e3aPSA\u5e94\u7b54\u7387\u3002<\/p>\n\n\n\n \u6620\u6069\u751f\u7269\u4e0eBioNTech\u8054\u5408\u5f00\u53d1\u7684B7-H3 ADC\u57282025\u5e74ASCO\u5e74\u4f1a\u4e0a\u516c\u5e03\u4e86I\/II\u671f\u4e34\u5e8a\u6570\u636e\u3002\u5728\u63a5\u53d7\u8fc7\u591a\u7ebf\u6cbb\u7597\u7684mCRPC\u60a3\u8005\u4e2d\uff0c\u786e\u8ba4\u5ba2\u89c2\u7f13\u89e3\u738730.8%\uff0c\u75be\u75c5\u63a7\u5236\u738790.4%\uff0c6\u4e2a\u6708rPFS\u738767.7%\u30022026\u5e74ASCO GU\u4e0a\u66f4\u65b0\u7684\u6570\u636e\u663e\u793a\uff0c\u5728\u4e2d\u4f4d\u65e2\u5f804\u7ebf\u6cbb\u7597\u7684146\u4f8bmCRPC\u60a3\u8005\u4e2d\uff0c\u4e2d\u4f4drPFS\u8fbe11.3\u4e2a\u6708\uff0c\u4e2d\u4f4dOS\u8fbe22.5\u4e2a\u6708\u3002\u8be5\u836f\u7269\u5df2\u83b7FDA\u5feb\u901f\u901a\u9053\u8ba4\u5b9a\uff0c\u5168\u7403\u5173\u952e\u6027III\u671f\u4e34\u5e8a\u8bd5\u9a8c\u6b63\u5728\u5f00\u5c55[6]<\/sup>\u3002<\/p>\n\n\n\n \u540c\u65f6\uff0cADC\u9776\u70b9\u6b63\u5728\u4eceB7-H3\u5411KLK2\u62d3\u5c55\u3002\u5f3a\u751f\u7684KLK2 ADC\uff08JNJ-98768111\uff09I\u671f\u8bd5\u9a8c\u5df2\u4e8e2026\u5e748\u6708\u542f\u52a8\uff0c\u8ba1\u5212\u5165\u7ec4100\u4f8b\u665a\u671f\u524d\u5217\u817a\u764c\u60a3\u8005\u3002<\/p>\n\n\n\n \u524d\u5217\u817a\u764c\u957f\u671f\u4ee5\u6765\u88ab\u8ba4\u4e3a\u662f\u514d\u75ab\u201c\u51b7\u80bf\u7624\u201d\uff0c\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u5728\u6b64\u9886\u57df\u666e\u904d\u672a\u80fd\u5c55\u73b0\u4e34\u5e8a\u6548\u7528\u3002T\u7ec6\u80de\u8854\u63a5\u5668\u53cc\u7279\u5f02\u6027\u6297\u4f53\u63d0\u4f9b\u4e86\u4e0d\u540c\u7684\u514d\u75ab\u6cbb\u7597\u601d\u8def\u3002<\/p>\n\n\n\n KLK2\u662f\u4e00\u79cd\u524d\u5217\u817a\u7279\u5f02\u6027\u5206\u6ccc\u578b\u4e1d\u6c28\u9178\u86cb\u767d\u9176\uff0c2025\u5e74\u53d1\u8868\u4e8eClinical Cancer Research\u7684\u7814\u7a76\u786e\u7acb\u4e86KLK2\u4f5c\u4e3a\u524d\u5217\u817a\u764c\u9ad8\u5ea6\u8c31\u7cfb\u7279\u5f02\u6027\u7ec6\u80de\u8868\u9762\u9776\u70b9\u7684\u5730\u4f4d[7]<\/sup>\u3002KLK2\u8868\u8fbe\u4e25\u683c\u4f9d\u8d56AR\uff0c\u5728AR\u9633\u6027\u80bf\u7624\u4e2d\u4e0ePSMA\u548cSTEAP1\u5171\u8868\u8fbe\uff0c\u4f46\u5728\u795e\u7ecf\u5185\u5206\u6ccc\u548c\u53cc\u9634\u6027\u8868\u578b\u4e2d\u57fa\u672c\u7f3a\u5931\u3002\u8fd9\u610f\u5473\u7740KLK2\u9776\u5411\u6cbb\u7597\u5929\u7136\u8986\u76d6AR\u9633\u6027\u80bf\u7624\uff0c\u4f46\u5bf9AR\u9634\u6027\/\u795e\u7ecf\u5185\u5206\u6ccc\u8f6c\u5316\u7684\u60a3\u8005\u65e0\u6548\u3002<\/p>\n\n\n\n \u5f3a\u751f\u7684Pasritamig\u662f\u9996\u4e2a\u9776\u5411KLK2\u7684T\u7ec6\u80de\u8854\u63a5\u5668\u53cc\u7279\u5f02\u6027\u6297\u4f53\u3002I\u671f\u7814\u7a76\u5165\u7ec4174\u4f8bmCRPC\u60a3\u8005\uff0c\u4e2d\u4f4d\u65e2\u5f80\u7cfb\u7edf\u6cbb\u7597\u7ebf\u6570\u4e3a4\u7ebf\u3002\u5728RP2D\u7597\u6548\u4eba\u7fa4\u4e2d\uff08n=33\uff09\uff0c\u4e2d\u4f4drPFS\u4e3a7.85\u4e2a\u6708\uff0c42.4%\uff0814\/33\uff09\u7684\u60a3\u8005\u5b9e\u73b0PSA50\u5e94\u7b54\u3002\u5b89\u5168\u6027\u65b9\u9762\uff0c\u7ec6\u80de\u56e0\u5b50\u91ca\u653e\u7efc\u5408\u5f81\u53d1\u751f\u7387\u4ec58.9%\uff0c\u4e14\u5168\u90e8\u4e3a1\u7ea7\uff0c\u53ef\u5728\u95e8\u8bca\u5b89\u5168\u7ed9\u836f[8]<\/sup>\u3002\u76ee\u524d\uff0cPasritamig\u6709\u4e24\u9879III\u671f\u8bd5\u9a8c\u5728\u8fdb\u884c\u4e2d\u3002<\/p>\n\n\n\n \u8bfa\u534e\u7684Pluvicto\uff08177<\/sup>Lu-PSMA-617\uff09\u5728III\u671fPSMAddition\u8bd5\u9a8c\u4e2d\uff0c\u5c06\u6cbb\u7597\u573a\u666f\u62d3\u5c55\u81f3mHSPC\u3002Pluvicto\u8054\u5408\u6807\u51c6\u6cbb\u7597\u5728PSMA\u9633\u6027mHSPC\u60a3\u8005\u4e2d\uff0c\u5c06\u5f71\u50cf\u5b66\u8fdb\u5c55\u6216\u6b7b\u4ea1\u98ce\u9669\u964d\u4f4e\u4e8628%\uff08HR 0.72\uff09\uff0c\u5b8c\u5168\u7f13\u89e3\u7387\u4ece42.3%\u63d0\u5347\u81f357.1%\u3002OS\u4e2d\u671f\u5206\u6790\u663e\u793aHR\u4e3a0.84\uff0895% CI 0.63-1.13\uff09\uff0c\u8d8b\u52bf\u6709\u5229\u4e8ePluvicto\u8054\u5408\u6cbb\u7597\u7ec4\uff0c\u4f46\u5c1a\u672a\u8fbe\u5230\u7edf\u8ba1\u5b66\u663e\u8457\u6027\uff0c\u6570\u636e\u4ecd\u5728\u6210\u719f\u4e2d\u3002<\/p>\n\n\n\n \u9700\u8981\u8bf4\u660e\u7684\u662f\uff0cmHSPC\u9002\u5e94\u75c7\u5c1a\u672a\u83b7\u6279\u30022025\u5e743\u670828\u65e5\uff0cFDA\u6269\u5c55\u6279\u51c6\u7684\u9002\u5e94\u75c7\u4e3aPSMA\u9633\u6027mCRPC\uff08\u65e2\u5f80\u63a5\u53d7\u8fc7ARPI\u6cbb\u7597\u3001\u9002\u5408\u5ef6\u8fdf\u7d2b\u6749\u70f7\u7c7b\u5316\u7597\u7684\u60a3\u8005\uff09\uff0c\u4f9d\u636e\u7684\u662fIII\u671fPSMAfore\u8bd5\u9a8c [9,10]<\/sup>\u3002PSMAfore\u6570\u636e\u663e\u793a\uff0cPluvicto\u76f8\u6bd4\u66f4\u6362ARPI\u5c06\u5f71\u50cf\u5b66\u8fdb\u5c55\u6216\u6b7b\u4ea1\u98ce\u9669\u964d\u4f4e\u4e8659%\uff08HR 0.41\uff09\uff0c\u4e2d\u4f4drPFS\u4e3a11.6\u4e2a\u6708 vs 5.6\u4e2a\u6708\u3002<\/p>\n\n\n\n Candel Therapeutics\u7684CAN-2409\u662f\u4e00\u79cd\u817a\u75c5\u6bd2\u4ecb\u5bfc\u7684\u57fa\u56e0\u7597\u6cd5\u3002III\u671fPrTK03\u8bd5\u9a8c\u5165\u7ec4745\u4f8b\u65b0\u8bca\u65ad\u7684\u4e2d\u9ad8\u5371\u5c40\u9650\u6027\u524d\u5217\u817a\u764c\u60a3\u8005\uff0c\u5728\u6807\u51c6\u653e\u7597\u57fa\u7840\u4e0a\u8054\u5408CAN-2409\u3002\u4e2d\u4f4d\u968f\u8bbf50.3\u4e2a\u6708\u65f6\uff0cCAN-2409\u7ec4\u5c06\u590d\u53d1\u6216\u6b7b\u4ea1\u98ce\u9669\u964d\u4f4e\u4e8630%\uff08HR 0.70\uff09\u3002\u6cbb\u7597\u540e2\u5e74\u6d3b\u68c0\u663e\u793a\uff0c\u6cbb\u7597\u7ec480.4%\u7684\u60a3\u8005\u8fbe\u5230\u75c5\u7406\u5b8c\u5168\u7f13\u89e3\uff0c\u663e\u8457\u9ad8\u4e8e\u5bf9\u7167\u7ec4\u768463.6%\u3002CAN-2409\u5df2\u88abFDA\u6388\u4e88\u518d\u751f\u533b\u5b66\u5148\u8fdb\u7597\u6cd5\u8ba4\u5b9a[11]<\/sup>\u3002<\/p>\n\n\n\n \u51e0\u4e4e\u6240\u6709\u5df2\u4e0a\u5e02\u7684AR\u62ee\u6297\u5242\u90fd\u9776\u5411\u540c\u4e00\u4e2a\u4f4d\u70b9\u2014\u2014\u914d\u4f53\u7ed3\u5408\u53e3\u888b\u3002<\/a>\u4e00\u65e6<\/a>LBD\u53d1\u751f\u7a81\u53d8\uff0cLBP\u6784\u8c61\u6539\u53d8\uff0c\u836f\u7269\u7ed3\u5408\u80fd\u529b\u4e0b\u964d\uff0c\u8010\u836f\u968f\u4e4b\u4ea7\u751f\u30022023\u5e74\uff0c\u6d59\u6c5f\u5927\u5b66\u56e2\u961f\u5728ACS Central Science\u4e0a\u9996\u6b21\u901a\u8fc7\u5206\u5b50\u52a8\u529b\u5b66\u6a21\u62df\u548c\u57fa\u4e8e\u7ed3\u6784\u7684\u865a\u62df\u7b5b\u9009\uff0c\u53d1\u73b0\u5e76\u9a8c\u8bc1\u4e86AR\u4e8c\u805a\u5316\u754c\u9762\u4e0a\u7684\u4e00\u4e2a\u5168\u65b0\u53e3\u888b\uff08DIP\uff09\uff0c\u5e76\u83b7\u5f97\u4e86\u9996\u4e2a\u9776\u5411\u8be5\u4f4d\u70b9\u7684\u5148\u5bfc\u5316\u5408\u7269M17-B15[12]<\/sup>\u3002<\/p>\n\n\n\n DIP-1018\u7531\u6d59\u6c5f\u5927\u5b66\u91d1\u534e\u7814\u7a76\u9662\u56e2\u961f\u7814\u53d1\uff0c\u5176IND\u7533\u8bf7\u5df2\u4e8e2026\u5e747\u6708\u83b7CDE\u627f\u529e\u3002<\/p>\n\n\n\n \u5728\u5b66\u672f\u7814\u7a76\u5c42\u9762\uff0cC13\u662f\u4e00\u79cd\u975e\u7ade\u4e89\u6027DIP\u7ed3\u5408\u5242\uff0cIC50\u4e3a0.010 \u03bcM\uff0c\u5728LNCaP\u5f02\u79cd\u79fb\u690d\u7624\u6a21\u578b\u4e2d\u53e3\u670d\u7ed9\u836f\u5b9e\u73b0\u4e86123.4%\u7684\u80bf\u7624\u751f\u957f\u6291\u5236\u7387[13]<\/sup>\u3002Y5\u5728\u540c\u671f\u520a\u53d1\u8868\uff0c\u5728DIP\u9776\u5411\u7684\u57fa\u7840\u4e0a\u5b9e\u73b0\u4e86\u53cc\u91cd\u4f5c\u7528\u673a\u5236\u2014\u2014\u65e2\u963b\u65adAR\u4e8c\u805a\u5316\uff0c\u53c8\u901a\u8fc7\u6cdb\u7d20-\u86cb\u767d\u9176\u4f53\u9014\u5f84\u8bf1\u5bfcAR\u86cb\u767d\u964d\u89e3[14]<\/sup>\u3002<\/p>\n\n\n\n \u9700\u8981\u6307\u51fa\u7684\u662f\uff0cDIP\u9776\u5411\u836f\u7269\u76ee\u524d\u5168\u90e8\u5904\u4e8e\u4e34\u5e8a\u524d\u9636\u6bb5\uff0c\u5c1a\u65e0\u4efb\u4f55\u4e34\u5e8a\u5f00\u53d1\u5148\u4f8b\u3002DIP\u662f\u5426\u662f\u4e00\u4e2a\u771f\u6b63\u201c\u53ef\u6210\u836f\u201d\u7684\u53e3\u888b\uff0c\u4ecd\u9700\u4e34\u5e8a\u8bd5\u9a8c\u6765\u56de\u7b54\u3002<\/p>\n\n\n\n \u5728\u7ec6\u80de\u6cbb\u7597\u65b9\u5411\uff0cPSMA CAR-T\u7684\u65e9\u671f\u63a2\u7d22\u540c\u6837\u63d0\u4f9b\u4e86\u503c\u5f97\u5173\u6ce8\u7684\u4fe1\u53f7\u3002P-PSMA-101\u7684I\u671f\u7814\u7a76\uff0c\u91c7\u7528\u975e\u75c5\u6bd2piggyBac\u6784\u5efa\u3001\u5e72\u7ec6\u80de\u8bb0\u5fc6T\u7ec6\u80de\uff08TSCM\uff09\u5bcc\u96c6\u548ciCasp9\u5b89\u5168\u5f00\u5173\u4e09\u9879\u5de5\u7a0b\u6539\u9020\u3002\u572833\u4f8b\u91cd\u5ea6\u9884\u5904\u7406\u7684mCRPC\u60a3\u8005\u4e2d\uff0c21%\uff087\/33\uff09\u5b9e\u73b0PSA50\u5e94\u7b54\uff0c2\u4f8b\u7f13\u89e3\u6301\u7eed\u8d85\u8fc712\u4e2a\u6708\uff0c\u5176\u4e2d1\u4f8b\u9aa8\u8f6c\u79fb\u7076\u6d3b\u68c0\u672a\u89c1\u80bf\u7624\u7ec6\u80de\uff0c\u4ec5\u89c1T\u7ec6\u80de\u6d78\u6da6\uff0c\u539f\u80bf\u7624\u90e8\u4f4d\u68c0\u6d4b\u5230CAR\u8f6c\u57fa\u56e0[15]<\/sup>\u3002<\/p>\n\n\n\n \u4f46\u5b89\u5168\u6027\u7a97\u53e3\u5f88\u7a84\uff1aCRS\u53d1\u751f\u738761%\uff0c24%\u7684\u60a3\u8005\u9700\u8981\u542f\u52a8\u5b89\u5168\u5f00\u5173\uff0c15%\u51fa\u73b0HLH\u6837\u6bd2\u6027\uff0c1\u4f8b\u6cbb\u7597\u76f8\u5173\u6b7b\u4ea1\u3002\u8be5\u8bd5\u9a8c\u4e8e2024\u5e749\u6708\u7ec8\u6b62[16]<\/sup>\u3002\u8fd9\u4e00\u7ed3\u679c\u63d0\u793a\uff0cCAR-T\u5728\u524d\u5217\u817a\u764c\u4e2d\u7684\u6838\u5fc3\u74f6\u9888\u4e0d\u5728\u4e8e\u9776\u70b9\u9009\u62e9\uff0c\u800c\u5728\u4e8e\u5982\u4f55\u5728\u7ef4\u6301\u6301\u4e45\u7f13\u89e3\u7684\u540c\u65f6\u63a7\u5236\u6bd2\u6027\u3002<\/p>\n\n\n\n \u4e0a\u8ff0\u8fdb\u5c55\u8986\u76d6\u4e86PROTAC\u964d\u89e3\u3001ADC\u7cbe\u51c6\u6295\u9012\u3001T\u7ec6\u80de\u8854\u63a5\u5668\u514d\u75ab\u6fc0\u6d3b\u3001\u653e\u5c04\u914d\u4f53\u7597\u6cd5\u3001\u57fa\u56e0\u7597\u6cd5\u3001DIP\u9776\u5411\u548cCAR-T\u7b49\u591a\u6761\u6280\u672f\u8def\u7ebf\uff0c\u4f46\u6240\u6709\u65b9\u5411\u90fd\u9762\u4e34\u540c\u4e00\u4e2a\u6839\u672c\u6027\u95ee\u9898\uff1a\u4ece\u4e34\u5e8a\u524d\u5230\u4e0a\u5e02\u7684\u6210\u529f\u7387\u6781\u4f4e\u3002<\/p>\n\n\n\n \u4ee5PROTAC\u4e3a\u4f8b\uff0cQLH12016\u7684PSA50\u5e94\u7b54\u7387\u7ea6\u4e3a20.5%\uff0cHP518\u7684I\u671f\u4ec53\u4f8bPSA50\u5e94\u7b54\uff0c\u5747\u5c5e\u4e8e\u65e9\u671f\u4fe1\u53f7\u3002ADC\u9886\u57df\u867d\u7136B7-H3\u9776\u70b9\u6570\u636e\u79ef\u6781\uff0c\u4f46ADC\u836f\u7269\u7684\u6cbb\u7597\u7a97\u53e3\u3001\u957f\u671f\u5b89\u5168\u6027\u3001\u8010\u836f\u673a\u5236\u5747\u9700\u8fdb\u4e00\u6b65\u7814\u7a76\u3002Pasritamig\u7684PSA50\u5e94\u7b54\u738742.4%\u5728\u672b\u7ebf\u4eba\u7fa4\u4e2d\u8868\u73b0\u7a81\u51fa\uff0c\u4f46\u6837\u672c\u91cf\u6709\u9650\uff0c\u9700\u66f4\u5927\u89c4\u6a21\u7814\u7a76\u786e\u8ba4\u3002P-PSMA-101\u7684\u8bd5\u9a8c\u7ec8\u6b62\u5219\u63d0\u9192\u6211\u4eec\uff0c\u5b9e\u4f53\u7624\u7ec6\u80de\u6cbb\u7597\u7684\u5b89\u5168\u6027\u548c\u53ef\u91cd\u590d\u6027\u4ecd\u662f\u5de8\u5927\u6311\u6218\u3002DIP\u9776\u5411\u836f\u7269\u8ddd\u79bb\u4e34\u5e8a\u9a8c\u8bc1\u8fd8\u6709\u66f4\u957f\u7684\u8def\u3002<\/p>\n\n\n\n <\/a>\u65e0\u8bba\u54ea\u6761\u8def\u7ebf\uff0c\u5173\u952e\u80fd\u7387\u5148\u5728\u4e34\u5e8a\u7814\u7a76\u4e2d\u8bc1\u660e\u603b\u751f\u5b58\u83b7\u76ca\u3002\u4ece\u6570\u636e\u6210\u719f\u5ea6\u770b\uff0c\u5f53\u524d\u5448\u73b0\u56db\u4e2a\u5c42\u6b21\uff1a<\/a><\/p>\n\n\n\n \u7b2c\u4e00\u5c42\uff0c\u5df2\u4e0a\u5e02\u836f\u7269\uff0c\u4f46OS\u5c1a\u5f85\u786e\u8bc1\u3002 Pluvicto\u5728\u5316\u7597\u524dmCRPC\u7684III\u671fPSMAfore\u4e2d\uff0crPFS\u6570\u636e\u6700\u4e3a\u786e\u8bc1\uff0811.6\u4e2a\u6708 vs 5.6\u4e2a\u6708\uff0cHR 0.41\uff09\uff0c\u4f46\u6700\u7ec8OS\u5206\u6790\u4e3a\u63a2\u7d22\u6027\u5206\u6790\uff0cHR 0.91\uff0895% CI 0.72-1.14\uff09\uff0c\u672a\u8fbe\u7edf\u8ba1\u5b66\u663e\u8457\u3002mHSPC\u9636\u6bb5\u7684PSMAddition\u540c\u6837rPFS\u9633\u6027\u3001OS\u672a\u6210\u719f\u3002<\/p>\n\n\n\n \u7b2c\u4e8c\u5c42\uff0c\u786e\u8bc1\u6027III\u671f\u8fdb\u884c\u4e2d\uff0c\u4ee5OS\u4e3a\u7ec8\u70b9\u3002 KLK2\u9776\u5411\u7684Pasritamig\u5df2\u6709\u4e24\u9879III\u671f\uff1aKLK2-comPAS\uff08\u5355\u836f vs BSC\uff09\u4e3b\u8981\u7ec8\u70b9\u4e3aOS\uff1bKLK2-PASenger\uff08\u8054\u5408\u591a\u897f\u4ed6\u8d5b\uff09\u53cc\u4e3b\u8981\u7ec8\u70b9\u4e3aOS\u548crPFS\u3002ADC\u65b9\u5411\uff0cDB-1311\/BNT324\u7684\u5168\u7403III\u671f\u5df2\u5b8c\u6210\u9996\u4f8b\u5165\u7ec4\u3002<\/p>\n\n\n\n \u7b2c\u4e09\u5c42\uff0c\u65e9\u671f\u4e34\u5e8a\u9a8c\u8bc1\u3002 PROTAC\u5df2\u6709\u591a\u4e2a\u5206\u5b50\u8fdb\u5165I\u671f\uff08GLR2037\u3001AZD9750\u3001HP518\u7b49\uff09\uff0c\u4f46\u6837\u672c\u91cf\u6709\u9650\u3001\u968f\u8bbf\u5c1a\u77ed\uff0c\u8ddd\u79bb\u786e\u8bc1\u6027\u7ec8\u70b9\u4ecd\u9700\u4e0d\u5c11\u65f6\u95f4\u3002<\/p>\n\n\n\n \u7b2c\u56db\u5c42\uff0c\u4e34\u5e8a\u524d\u6216\u9996\u6b21\u4eba\u4f53\u8bd5\u9a8c\u95e8\u69db\u3002 DIP<\/a>\u9776\u5411\u836f\u7269\u5168\u90e8\u5904\u4e8e\u4e34\u5e8a\u524d\uff1bCAR-T\u65b9\u5411\uff0cP-PSMA-101\u8bd5\u9a8c\u5df2\u4e8e2024\u5e74\u7ec8\u6b62\u3002\u8fd9\u4e24\u6761\u8def\u7ebf\u9762\u4e34\u7684\u662f\u4ece\u4e34\u5e8a\u524d\/\u9996\u6b21\u4eba\u4f53\u5230\u786e\u8bc1\u6027\u4e34\u5e8a\u7684\u8de8\u8d8a\u3002<\/a>\u8fd9\u4e00\u8de8\u8d8a\u6b63\u662f\u5c0f\u725b\u533b\u836f\u663e\u8eab\u624b\u4e4b\u5904\uff0c<\/a>\u6211\u4eec\u5728\u9996\u6b21\u4eba\u4f53\u8bd5\u9a8c\u65b9\u6848\u8bbe\u8ba1\u3001\u5242\u91cf\u9012\u589e\u4e0eDLT\u8bc4\u4f30\u3001\u751f\u7269\u6807\u5fd7\u7269\u9a71\u52a8\u7684\u60a3\u8005\u7b5b\u9009\u7b49\u5173\u952e\u73af\u8282\u5177\u5907\u5b8c\u6574\u80fd\u529b\uff0c\u52a9\u529b\u7533\u529e\u65b9\u5728\u8fd9\u4e00\u9ad8\u98ce\u9669\u9636\u6bb5\u964d\u4f4e\u8bd5\u9519\u6210\u672c\u3001\u52a0\u901f\u4e34\u5e8a\u63a8\u8fdb\u3002<\/p>\n\n\n\n \u8fd9\u4e9b\u8fdb\u5c55\u5171\u540c\u4f20\u9012\u7684\u4fe1\u606f\u662f\uff1a\u524d\u5217\u817a\u764c\u8010\u836f\u4e0d\u518d\u662f\u201c\u65e0\u836f\u53ef\u7528\u201d\u7684\u7ec8\u70b9\uff0c\u800c\u6b63\u5728\u6210\u4e3a\u4e00\u4e2a\u6709\u591a\u79cd\u673a\u5236\u53ef\u88ab\u5e72\u9884\u7684\u6cbb\u7597\u8282\u70b9\u3002<\/p>\n\n\n\n [1] Antonarakis ES, et al. Prevalence and Spectrum of AR Ligand-Binding Domain Mutations Detected in Circulating-Tumor DNA Across Disease States in Men With Metastatic Castration-Resistant Prostate Cancer. JCO Precision Oncology<\/em>. 2024;8:e2300330. doi:10.1200\/PO.23.00330.<\/p>\n\n\n\n [2] Zhang S, et al. Phase 1 Study of QLH12016, an Androgen Receptor PROTAC Degrader in Heavily Pretreated Patients with mCRPC: Safety, Tolerability, and Antitumor Activity. ESMO 2025, Abstract 2450P. As of data cutoff July 1, 2025.<\/p>\n\n\n\n [3] \u9f50\u9c81\u5236\u836f. QLH12016\u57282025 ESMO\u5927\u4f1a\u53d1\u5e03\u2160\u671f\u6570\u636e\uff0cPROTAC\u6280\u672f\u7834\u5c40mCRPC\u8010\u836f\u56f0\u5c40. \u6469\u71b5\u533b\u836f. 2025\u5e7410\u6708.<\/p>\n\n\n\n [4] Azad AA, Gurney H, Voskoboynik M, et al. Phase 1 study of HP518, a PROTAC AR degrader in patients with mCRPC: results on safety, pharmacokinetics, and anti-tumor activity. Investigational New Drugs<\/em>. 2025;43(2):435-445. doi:10.1007\/s10637-025-01533-8.<\/p>\n\n\n\n [5] Monte Rosa Therapeutics. Updated Clinical Data from Phase 1\/2 Study of MRT-2359 in Combination with Enzalutamide in Heavily Pretreated mCRPC Patients. ASCO GU 2026. February 24, 2026.<\/p>\n\n\n\n [6] BioNTech\/\u6620\u6069\u751f\u7269. DB-1311\/BNT324 Phase 1\/2 Data in mCRPC. 2025 ASCO Annual Meeting. NCT05914116.<\/p>\n\n\n\n [7] Shen F, Smith R, McDevitt T, et al. Human Kallikrein 2: A Novel Lineage-Specific Surface Target in Prostate Cancer. Clinical Cancer Research<\/em>. 2025;31(21):4543-4556. doi:10.1158\/1078-0432.CCR-25-0950.<\/p>\n\n\n\n [8] Stein MN, Vinceneux A, Robbrecht D, et al. Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase I Study. Journal of Clinical Oncology<\/em>. 2025;43(22):2515-2526. doi:10.1200\/JCO-25-00678.<\/p>\n\n\n\n [9] FDA. FDA expands Pluvicto\u2019s metastatic castration-resistant prostate cancer indication. March 28, 2025.<\/p>\n\n\n\n [10] Urology Times. FDA approves expanded label for 177Lu-PSMA-617 in mCRPC. March 28, 2025.<\/p>\n\n\n\n [11] Gejerman G, et al. Phase 3, Randomized, Placebo Controlled Clinical Trial of CAN-2409+Prodrug in Combination with Standard of Care External Beam Radiation (EBRT) for Newly Diagnosed Localized Prostate Cancer. ASTRO 2025, Abstract 114.<\/p>\n\n\n\n [12] Fu W, Yang H, Hu C, et al. Small-Molecule Inhibition of Androgen Receptor Dimerization as a Strategy against Prostate Cancer. ACS Central Science<\/em>. 2023;9(4):675-684. doi:10.1021\/acscentsci.2c01548.<\/p>\n\n\n\n [13] Liao J, et al. Discovery of N-(thiazol-2-yl) Furanamide Derivatives as Potent Orally Efficacious AR Antagonists with Low BBB Permeability. Journal of Medicinal Chemistry<\/em>. 2025. doi:10.1021\/acs.jmedchem.5c02089.<\/p>\n\n\n\n [14] Discovery of N-(1,2,4-Thiadiazol-5-yl)benzo[b]oxepine-4-carboxamide Derivatives as Novel Antiresistance Androgen Receptor Antagonists. Journal of Medicinal Chemistry<\/em>. 2025;68(3):3445-3459. doi:10.1021\/acs.jmedchem.4c02649.<\/p>\n\n\n\n [15] Slovin SF, Gao X, Wei XX, et al. Phase 1 Trial of P-PSMA-101 CAR-T Cells in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC). Clinical Cancer Research<\/em>. Published online March 4, 2026. doi:10.1158\/1078-0432.CCR-25-3052. [16] ClinicalTrials.gov. NCT04249947: P-PSMA-101 CAR-T Cells in the Treatment of Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Advanced Salivary Gland Cancers (SGC). Status: Terminated. Primary Completion Date: September 30, 2024.<\/p>\n\n\n\n <\/p>\n\n\n\n <\/p>\n\n\n\n \u64b0\u6587\uff1a\u90d1\u53f6\u654f<\/p>\n\n\n\n <\/p>\n","protected":false},"excerpt":{"rendered":" \u96c4\u6fc0\u7d20\u53d7\u4f53\uff08AR\uff09\u4fe1\u53f7\u901a\u8def\u662f\u524d\u5217\u817a\u764c\u7684\u6838\u5fc3\u9a71\u52a8\u56e0\u7d20\u3002\u7b2c\u4e8c\u4ee3AR\u901a\u8def\u6291\u5236\u5242\u663e\u8457\u5ef6\u957f\u4e86\u60a3\u8005\u751f\u5b58\uff0c\u4f46\u51e0\u4e4e\u6240\u6709\u60a3\u8005\u6700\u7ec8\u90fd\u4f1a\u56e0AR\u901a\u8def\u5f02\u5e38\u6fc0\u6d3b\u800c\u51fa\u73b0\u8010\u836f\u3002\u771f\u5b9e\u4e16\u754c\u6570\u636e\u663e\u793a\uff0cAR\u914d\u4f53\u7ed3\u5408\u57df\uff08LBD\uff09\u7a81\u53d8\u5728\u672a\u63a5\u53d7\u8fc7\u7b2c\u4e8c\u4ee3ARPI\u6cbb\u7597\u8005\u4e2d\u60a3\u75c5\u7387\u4e3a15%\uff0c\u63a5\u53d7\u4e00\u7ebf\u6cbb\u7597\u540e\u4e3a22%\uff0c\u63a5\u53d7\u4e24\u7ebf\u6cbb\u7597\u540e\u4e3a24% [1]\u3002\u8010\u836f\u673a\u5236\u6781\u4e3a\u590d\u6742\uff0c\u65e2\u5305\u542bAR\u4f9d\u8d56\u6027\u9014\u5f84\uff08AR\u57fa\u56e0\u6269\u589e\u3001\u70b9\u7a81\u53d8\u3001AR\u526a\u63a5\u53d8\u5f02\u4f53\uff09\uff0c\u4e5f\u6d89\u53caAR\u975e\u4f9d\u8d56\u9014\u5f84\uff08\u795e\u7ecf\u5185\u5206\u6ccc\u5206\u5316\u3001\u65c1\u8def\u4fe1\u53f7\u6fc0\u6d3b\u3001\u8c31\u7cfb\u53ef\u5851\u6027\uff09\u3002\u4e8c\u3001\u7cbe\u51c6\u6295\u9012\uff1aADC\u836f\u7269\u91cd\u5851\u8010\u836f\u80bf\u7624\u7684\u6cbb\u7597\u683c\u5c40<\/h5>\n\n\n\n
\u4e09\u3001T\u7ec6\u80de\u8854\u63a5\u5668\uff1a\u6253\u7834\u524d\u5217\u817a\u764c\u201c\u51b7\u80bf\u7624\u201d\u514d\u75ab\u5c4f\u969c<\/h5>\n\n\n\n
\u56db\u3001\u653e\u5c04\u914d\u4f53\u7597\u6cd5\uff1a\u4ece\u672b\u7ebf\u8d70\u5411\u66f4\u65e9\u671f<\/h5>\n\n\n\n
\u4e94\u3001\u57fa\u56e0\u7597\u6cd5\u4e0e\u514d\u75ab\u6fc0\u6d3b\uff1a\u4ece\u201c\u51b7\u201d\u5230\u201c\u70ed\u201d\u7684\u8f6c\u5316<\/h5>\n\n\n\n
\u516d\u3001\u5168\u65b0\u673a\u5236\u63a2\u7d22\uff1aAR\u4e8c\u805a\u5316\u754c\u9762\u53e3\u888b\uff08DIP\uff09\u9776\u5411\u7b56\u7565<\/h5>\n\n\n\n
\u4e03\u3001\u7ec6\u80de\u6cbb\u7597\uff1aPSMA CAR-T\u7684\u65e9\u671f\u63a2\u7d22<\/h5>\n\n\n\n
\u516b\u3001\u7406\u6027\u5224\u65ad\uff1a\u591a\u6761\u6280\u672f\u8def\u7ebf\uff0c\u4e00\u4e2a\u5171\u540c\u74f6\u9888<\/h5>\n\n\n\n
\u53c2\u8003\u6587\u732e<\/h5>\n\n\n\n
\n\u9762\u5bf9\u8fd9\u4e00\u56f0\u5c40\uff0c\u5168\u7403\u521b\u65b0\u836f\u7814\u53d1\u6b63\u5728\u591a\u6761\u6218\u7ebf\u4e0a\u540c\u65f6\u63a8\u8fdb\u30022025\u81f32026\u5e74\u95f4\uff0c\u591a\u9879\u5177\u6709\u91cc\u7a0b\u7891\u610f\u4e49\u7684\u4e34\u5e8a\u6570\u636e\u9646\u7eed\u516c\u5e03\uff0c\u6807\u5fd7\u7740\u524d\u5217\u817a\u764c\u8010\u836f\u6cbb\u7597\u6b63\u4ece\u201c\u5835\u4f4f\u4e00\u4e2a\u9776\u70b9\u201d\u8d70\u5411\u201c\u591a\u673a\u5236\u534f\u540c\u6253\u51fb\u201d\u3002<\/p>\n","protected":false},"author":1,"featured_media":2158,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[147],"tags":[35,86,15,32,34],"class_list":["post-2156","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-147","tag-35","tag-86","tag-15","tag-32","tag-34"],"_links":{"self":[{"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/posts\/2156","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2156"}],"version-history":[{"count":1,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/posts\/2156\/revisions"}],"predecessor-version":[{"id":2157,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/posts\/2156\/revisions\/2157"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=\/wp\/v2\/media\/2158"}],"wp:attachment":[{"href":"https:\/\/www.millibuff.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2156"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2156"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.millibuff.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2156"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}