Targeting BCL2-Proteins for the Treatment of Solid Tumours

<table>The BCL2-family. The multidomain proapoptotic proteins BAX and BAK mediate the release of cytochrome c from mitochondria into cytosol. They are inhibited by the antiapoptotic BCL2-proteins (BCL2, <svg height="12.4339pt" id="M10" style="vertical-align:-3.31356pt" version="1.1" viewbox="-0.0498162 -9.12034 43.9595 12.4339" width="43.9595pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path d="M372 352C427 368 507 407 507 502C507 548 486 592 451 616C420 638 376 650 301 650H44V622C124 616 128 610 128 527V123C128 40 122 34 36 28V0H257C336 0 402 12 453 40C512 72 548 124 548 191C548 291 471 335 372 350V352ZM213 362V558C213 591 216 602 226 608C235 614 258 618 282 618C377 618 415 558 415 490C415 406 369 362 260 362H213ZM213 328H258C380 328 450 283 450 181C450 76 377 35 296 34C231 34 213 53 213 125V328Z" id="g190-67"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="588" vert-adv-y="588"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,8.238,0)"><path d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z" id="g190-68"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="665" vert-adv-y="665"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,17.248,0)"><path d="M495 163C480 117 462 85 444 65C421 39 387 34 332 34C290 34 256 36 236 47C218 57 213 77 213 131V526C213 612 222 616 301 622V650H40V622C122 616 128 611 128 526V126C128 41 120 34 36 28V0H489C498 31 519 126 525 157L495 163Z" id="g190-77"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="538" vert-adv-y="538"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,24.414,0)"><path d="M300 253H71L57 198H286L300 253Z" id="g190-46"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="356" vert-adv-y="356"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,29.347,0)"><path d="M655 0V28C585 35 563 50 517 120C469 193 414 280 360 366C427 469 460 516 481 545C526 604 545 614 619 622V650H391V622C457 614 462 604 438 560C411 511 381 463 339 398C295 466 258 523 225 580C210 606 211 615 272 622V650H26V622C98 614 111 603 154 538C189 482 235 408 288 324C200 188 149 116 124 85C95 47 64 34 7 28V0H236V28C169 36 164 46 188 89C220 148 261 217 310 291C372 193 417 118 442 77C461 44 454 35 392 28V0H655Z" id="g190-89"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="654" vert-adv-y="654"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,38.24,3.264)"><path d="M495 163C480 117 462 85 444 65C421 39 387 34 332 34C290 34 256 36 236 47C218 57 213 77 213 131V526C213 612 222 616 301 622V650H40V622C122 616 128 611 128 526V126C128 41 120 34 36 28V0H489C498 31 519 126 525 157L495 163Z" id="g190-77"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="538" vert-adv-y="538"></glyph.data></g></svg>, BCL-w, MCL1, and BCL2A1). BH3-only proteins (e.g., BIM, BID, PUMA, BAD, BMF, and NOXA) can neutralize the function of the antiapoptotic BCL2-proteins and may also directly activate BAX and BAK.</table>

Advances in Medicine

Targeting BCL2-Proteins for the Treatment of Solid Tumours

Figure 2