Compositions and methods for sensitizing low responsive tumors to cancer therapy

A method for enhancing the efficacy of tumor chemotherapy, radiation therapy or radionuclide therapy agent through a priori activation of apoptosis pathways of tumors, ‘AAAPT’, said method comprising administration to a patient with a tumor

• (a) a bioconjugate of Formula 3,
• and
• (b) a chemotherapeutic agent, a radiation therapy agent, or a radionuclide therapy agent;
• wherein
• T is a somatostatin receptor binding agent or a cathepsin B binding agent;
• L is —NH(CH2)bCO—, —OC(CH2)cNH—, —(CH2)dNH—, —HN(CH2)e—, —O(CH2)f(CH2CH2O)g(CH2)hO—, —HN(CH2)i(CH2CH2O)j(CH2)kNH— or -(AA)n-, wherein AA is a dipeptide;
• subscripts ‘b’, ‘c’, ‘d’ and ‘e’ independently vary from 1-10;
• subscripts ‘f’, ‘g’, ‘h’, ‘i’, ‘j and ‘k’ are independently vary from 1-100;
• subscript ‘n’ varies from 1 to 10;
• R1 is C1-C20 straight or branched alkyl, C3-C20 cycloalkyl, C1-C20 straight or branched alkenyl, C5-C10 alkyl, or C5-C20 arylalkyl;
• each of R2, R3 and R4 is independently hydrogen or methyl;
• said chemotherapy agent comprises doxorubicin, Bevacizumab, epirubicin, paclitaxel, docetaxel, 5-fluorouracil, cyclophosphamide, cisplatin, carboplatin, vinorelbine, capecitabine, liposomal doxorubicin, gemcitabine, ixabepilone, albumin-bound paclitaxel, eribulin, irinotecan, etoposide, vinblastine, tamoxifen, methotrexate or pemetrexed;
• said radiation therapy is external beam radiation;
• and
• said radionuclide therapy agent comprises 123I, 125I, 131I, 186/188Re, 111In, 177Lu, 153Sm, 89Sr, 90Y, 201Pb, 32P, 198Au, 165Dy, 80mBr, 67Cu or 117Sn.