Alamomin Ciwon Daji

**Alamomin Ciwon Daji** Ya kasan ce, kuma sune asalin damar ilimin halitta guda shida da aka samu a yayin haɓaka ciwace-ciwacen ɗan adam, kuma tun daga lokacin an ƙaru zuwa ƙarfin takwas da damar iya ba da damar guda biyu. Douglas Hanahan da Robert Weinberg ne suka kirkiro ra'ayin a cikin takardar su *The* *Hallmarks of Cancer da* aka buga Janairu 2000 a cikin Cell.

Waɗannan alamomin sun zama ƙa'idar tsari don daidaitawa da rikitarwar cututtukan neoplastic. Sun haɗa da ci gaba da siginar yaɗuwa, guje wa masu hana haɓaka girma, tsayayya da mutuwar tantanin halitta, ba da damar dawwama, haifar da angiogenesis, da kunna mamayewa da metastasis. Ƙarƙashin waɗannan alamomi sune rashin zaman lafiya na kwayoyin halitta, wanda ke haifar da bambancin kwayoyin halitta wanda ke hanzarta samun su, da kumburi, wanda ke haɓaka ayyuka masu yawa. Bugu da ƙari ga ƙwayoyin cutar kansa, ciwace-ciwacen daji suna nuna wani nau'i na rikitarwa: sun haɗa da al'umma na daukar aiki, masu yiwuwa kwayoyin halitta na yau da kullum waɗanda ke ba da gudummawa ga siyan halaye masu mahimmanci ta hanyar ƙirƙirar " ƙananan ƙwayar cuta ." Amincewa da yawaitar amfani da waɗannan ra'ayoyin zai ƙara yin tasiri ga haɓaka sabbin hanyoyin magance cutar kansar ɗan adam.

A cikin sabuntawar da aka buga a cikin 2011 ("Alamomin ciwon daji: ƙarni na gaba"), Weinberg da Hanahan sun ba da shawarar sabbin alamomi guda biyu: (1) hanyoyin rayuwa mara kyau da (2) guje wa tsarin rigakafi, da halaye biyu masu kunnawa: (1) genome rashin zaman lafiya, da (2) kumburi.

## '''Jerin alamomin'''

Kwayoyin cutar daji suna da lahani a cikin hanyoyin sarrafawa waɗanda ke sarrafa sau nawa suke rarraba, kuma a cikin tsarin amsawa waɗanda ke daidaita waɗannan hanyoyin sarrafawa (watau lahani a cikin homeostasis ).

Kwayoyin al'ada suna girma kuma suna rarraba, amma suna da iko da yawa akan wannan haɓakar. Suna girma ne kawai lokacin da abubuwan haɓaka suka motsa su. Idan sun lalace, birki na kwayoyin zai hana su rarrabawa har sai an gyara su. Idan ba za a iya gyara su ba, suna yin tsarin mutuwar kwayar halitta (apoptosis). Za su iya raba iyakacin adadin lokuta kawai. Sun kasance ɓangare na tsarin nama, kuma suna zama a inda suke. Suna buƙatar samar da jini don girma.

Duk waɗannan hanyoyin dole ne a shawo kan su don haɓakar tantanin halitta ya zama ciwon daji. Kowane tsari yana sarrafa sunadaran sunadaran da yawa. Dole ne furotin mai mahimmanci ya yi rauni a kowane ɗayan waɗannan hanyoyin. Wadannan sunadaran suna zama marasa aiki ko rashin aiki lokacin da jerin DNA na kwayoyin halittarsu ya lalace ta hanyar samu ko maye gurbi (maye gurbin da ba a gada ba amma yana faruwa bayan daukar ciki). Wannan yana faruwa a cikin jerin matakai, waɗanda Hanahan da Weinberg suke magana a matsayin alamomi.

### Wadatar kai a cikin alamun girma

: Kwayoyin ciwon daji ba sa buƙatar ƙarfafawa daga siginar waje (a cikin nau'i na abubuwan girma ) don ninka.

Yawanci, ƙwayoyin jiki suna buƙatar hormones da sauran kwayoyin halitta waɗanda ke aiki azaman sigina don girma da rarraba . Kwayoyin ciwon daji, duk da haka, suna da ikon girma ba tare da waɗannan sigina na waje ba. Akwai hanyoyi da yawa waɗanda kwayoyin cutar kansa zasu iya yin haka: ta hanyar samar da waɗannan sigina da kansu, wanda aka sani da alamar autocrine ; ta hanyar kunna hanyoyin sigina na dindindin waɗanda ke amsa waɗannan sigina; ko ta hanyar lalata 'kashe masu kunnawa' wanda ke hana haɓakar girma daga waɗannan sigina ( ra'ayi mara kyau ). Bugu da kari, rarrabuwar tantanin halitta a al'ada, sel marasa ciwon daji ana sarrafa su sosai. A cikin ƙwayoyin cutar kansa, waɗannan hanyoyin suna raguwa saboda sunadaran da ke sarrafa su suna canzawa, suna haifar da haɓaka girma da rarraba tantanin halitta a cikin ƙwayar cuta.

### Rashin hankali ga sigina na hana girma

: Kwayoyin ciwon daji gabaɗaya suna da juriya ga sigina masu hana girma daga maƙwabtansu.

Don sarrafa rarrabuwar tantanin halitta, sel suna da matakai a cikin su waɗanda ke hana haɓakar tantanin halitta da rarrabawa. Ana tsara waɗannan hanyoyin ta hanyar sunadaran da aka sani da ƙwayoyin cuta masu hana ƙari . Wadannan kwayoyin halitta suna ɗaukar bayanai daga tantanin halitta don tabbatar da cewa ya shirya don rarraba, kuma za su dakatar da rarraba idan ba haka ba (lokacin da DNA ta lalace, misali). A cikin ciwon daji, waɗannan sunadaran sunadaran ƙwayoyin cuta suna canza su don kada su hana rarrabawar kwayar halitta yadda ya kamata, ko da lokacin da tantanin halitta yana da matsala mai tsanani. Wata hanyar da sel ke hana rarrabuwar kawuna ita ce sel na yau da kullun suma za su daina rarrabuwa a lokacin da sel suka cika sararin da suke ciki kuma su taɓa wasu sel; aka sani da hana lamba . Kwayoyin cutar daji ba su da hana lamba, don haka za su ci gaba da girma da rarrabuwa, ba tare da la'akari da kewayen su ba.

### Kaucewa shirin mutuwa tantanin halitta

: *Apoptosis* wani nau'i ne na tsarin mutuwar tantanin halitta (kwayoyin kashe kansa),ya kuma kasan ce tsarin da ake tsara sel su mutu idan sun lalace. Kwayoyin ciwon daji suna iya keɓance wannan tsarin.

Kwayoyin suna da ikon 'hala kansu'; wani tsari da aka sani da apoptosis . Ana buƙatar wannan don kwayoyin halitta suyi girma da haɓaka yadda ya kamata, don kiyaye kyallen jikin jiki, kuma ana farawa lokacin da tantanin halitta ya lalace ko ya kamu da cutar. Kwayoyin ciwon daji, duk da haka, sun rasa wannan ikon; ko da yake sel na iya zama na rashin al'ada sosai, ba sa shan apoptosis. Kwayoyin ciwon daji na iya yin haka ta hanyar canza hanyoyin da ke gano lalacewa ko rashin daidaituwa. Wannan yana nufin cewa siginar da ta dace ba zata iya faruwa ba, don haka apoptosis ba zai iya kunnawa ba. Hakanan suna iya samun lahani a cikin siginar ƙasa da kanta, ko sunadaran da ke cikin apoptosis, kowannensu kuma zai hana apoptosis mai kyau.

### Yiwuwar kwafi mara iyaka

: Kwayoyi marasa ciwon daji suna mutuwa bayan wasu adadin rarrabuwa. Kwayoyin ciwon daji sun tsere daga wannan iyaka kuma a fili suna iya girma da rarrabuwa mara iyaka ( dauwama ). Amma waɗancan ƙwayoyin da ba su mutu ba sun lalata ƙwayoyin chromosomes, waɗanda za su iya zama cutar kansa.

Kwayoyin jiki ba su da ikon rarraba har abada. Suna da iyakataccen adadin rarrabuwa kafin sel su kasa rarraba ( senescence ), ko mutu (rikicin). Dalilin kuma waɗan nan shingen shi ne da farko saboda DNA a ƙarshen chromosomes, wanda aka sani da telomeres . Telomeric DNA yana gajarta tare da kowane rabo na tantanin halitta, har sai ya zama gajere yana kunna jin daɗi, don haka tantanin halitta ya daina rarrabawa. Kwayoyin ciwon daji suna ƙetare wannan shinge ta hanyar sarrafa enzymes (telomerase) don ƙara tsawon telomeres. Don haka, za su iya rarraba har abada, ba tare da fara jin daɗi ba.

Kwayoyin dabbobi masu shayarwa suna da wani shiri na zahiri, iyakar Hayflick, wanda ke iyakance haɓakar su zuwa kusan 60-70 ninki biyu, a wannan lokacin suna isa matakin jin daɗi.

Za'a iya shawo kan wannan iyaka ta hanyar kashe su pRB da p53 sunadaran sunadaran ƙwayar cuta, wanda ya ba su damar ci gaba da ninka har sai sun kai ga wani mataki da ake kira rikici, tare da apoptosis, karyotypic disarray, da kuma lokaci-lokaci (10 -7 ) fitowar tantanin halitta marar mutuwa wanda zai iya. ninki biyu ba tare da iyaka ba. Yawancin ƙwayoyin ciwon daji ba su dawwama.

Na'urar kirgawa ga tantanin halitta ninki biyu shine telomere, wanda ke raguwa a girman (rasa nucleotides a ƙarshen chromosomes) yayin kowace tantanin halitta. Kusan kashi 85 cikin 100 na masu ciwon daji suna daidaita telomerase don tsawaita telomeres kuma sauran 15% suna amfani da hanyar da ake kira Alternative Lengthening of Telomeres.

### Angiogenesis mai dorewa

: *Angiogenesis* shine tsarin da ake samar da sababbin hanyoyin jini. Kwayoyin cutar daji suna bayyana suna iya fara wannan tsari, suna tabbatar da cewa irin waɗannan ƙwayoyin suna samun isashshen iskar oxygen da sauran abubuwan gina jiki.

Nassoshin jiki na yau da kullun suna da tasoshin jini da ke gudana ta cikin su waɗanda ke isar da iskar oxygen daga huhu. Dole ne sel su kasance kusa da tasoshin jini don samun isassun iskar oxygen domin su tsira. Sabbin hanyoyin jini suna samuwa a lokacin haɓakar embryos, yayin gyaran rauni da kuma lokacin sake zagayowar haihuwa na mace. Ciwon daji mai faɗaɗa yana buƙatar sabbin hanyoyin jini don isar da isassun iskar oxygen zuwa ƙwayoyin cutar kansa, don haka yana amfani da waɗannan tsarin tsarin ilimin halittar jiki na yau da kullun don amfanin sa. Don yin wannan, ƙwayoyin cutar kansa suna samun ikon tsara samar da sabbin vasculature ta hanyar kunna 'canjin angiogenic'. A yin haka, suna sarrafa ƙwayoyin da ba su da ciwon daji waɗanda ke cikin ƙwayar cuta da ke iya haifar da jijiyoyin jini ta hanyar rage samar da abubuwan da ke hana samar da jini, da haɓaka samar da abubuwan da ke haɓaka samuwar jini.

### Ciwon nama da metastasis

: Kwayoyin ciwon daji na iya watsewa daga rukunin yanar gizon su ko sashin asalinsu don mamaye nama da ke kewaye da kuma yada ( *metastasize* ) zuwa sassan jiki mai nisa.

Ɗaya daga cikin sanannun kaddarorin ƙwayoyin cutar kansa shine ikon su na mamaye ƙwayoyin maƙwabta. Shi ne abin da ke nuna ko ƙwayar cuta ba ta da kyau ko mara kyau, kuma ita ce dukiyar da ke ba da damar yada su a jiki. Kwayoyin ciwon daji dole ne su fuskanci sauye-sauye masu yawa domin su sami ikon yin metastasize, a cikin tsari mai yawa wanda ke farawa da mamaye gida na sel cikin kyallen da ke kewaye. Sannan dole ne su mamaye magudanar jini, su tsira a cikin mummunan yanayi na tsarin jini, su fita daga wannan tsarin sannan su fara rarrabuwa cikin sabon nama.

## Sabuntawa
A cikin jawabin taron NCRI na 2010, Hanahan ya ba da shawarar sabbin alamomi guda biyu masu tasowa da halaye biyu masu kunnawa. An haɗa waɗannan daga baya a cikin sabunta labarin bita mai suna "Hallmarks of Cancer: the next generation."

### Alamomi masu tasowa

#### Deregulated metabolism
Yawancin kwayoyin cutar kansa suna amfani da madadin hanyoyin rayuwa don samar da makamashi, gaskiyar da aka yaba tun farkon karni na ashirin tare da ƙaddamar da hasashe na Warburg,   amma yanzu kawai samun sabon sha'awar bincike. Kwayoyin ciwon daji da ke nuna tasirin Warburg suna haɓaka glycolysis da fermentation na lactic acid a cikin cytosol kuma suna hana mitochondria kammala numfashi na aerobic na yau da kullun (oxidation na pyruvate, da citric acid sake zagayowar, da sarkar jigilar lantarki ). Maimakon cikakken oxidizing glucose don samar da yawan ATP mai yiwuwa, ƙwayoyin kansa sun gwammace su canza pyruvate zuwa tubalan ginin don ƙarin sel. A gaskiya ma, ƙananan ATP: ADP rabon da wannan tasiri ya haifar yana iya taimakawa wajen kashe mitochondria. Mitochondrial membrane m yana da hyperpolarized don hana ƙarfin lantarki-m permeability canjin pores (PTP) daga jawo apoptosis .

Ana bincikar cin abinci na ketogenic a matsayin maganin adjuvant don wasu cututtuka, ciki har da glioma,saboda rashin iyawar ciwon daji a cikin metabolizing jikin ketone .

#### Kaucewa tsarin rigakafi
Duk da ciwon daji da ke haifar da ƙãra kumburi da angiogenesis, sun kuma bayyana cewa za su iya guje wa hulɗa tare da tsarin garkuwar jiki ta hanyar asarar interleukin-33. (Duba rigakafin cutar kansa )

### Halayen Haɓakawa
Takardar da aka sabunta ta kuma gano halaye biyu masu tasowa. Waɗannan ana lakafta su kamar haka tunda samun su yana haifar da haɓakar “alamomi” da aka ɗauka.

#### Rashin kwanciyar hankali
Kwayoyin ciwon daji gabaɗaya suna da matsanancin rashin daidaituwa na chromosomal wanda ke daɗa muni yayin da cutar ke ci gaba. Kwayoyin HeLa, alal misali, suna da haɓaka sosai kuma suna da tetraploidy 12, trisomy 6, 8, da 17, da lambar chromosome na modal na 82 (maimakon adadin diploid na al'ada na 46). Ƙananan maye gurbi shine mafi kusantar abin da zai fara tumorigenesis, amma da zarar sel sun fara sake zagayowar-fusion-gada (BFB), za su iya canzawa a cikin sauri da sauri. (Dubi rashin zaman lafiyar kwayoyin halitta )

#### Kumburi
Abubuwan da aka gano na baya-bayan nan sun nuna rawar da kumburin gida ke takawa wajen haifar da nau'ikan ciwon daji da yawa. Kumburi yana haifar da angiogenesis da ƙarin amsawar rigakafi. Lalacewar matrix na waje da ake buƙata don samar da sabbin hanyoyin jini yana ƙara rashin daidaituwar metastasis. (Duba kumburi a cikin ciwon daji )

## Suka
Wani labarin a cikin *Nature Reviews Cancer* a shekara ta 2010 ya nuna cewa biyar daga cikin 'alamomin' suma suna da halayyar ciwace-ciwacen daji . Alamar mugunyar cuta ɗaya ce ita ce ikonta na mamayewa da daidaitawa .

Wani labarin a cikin *Journal of Biosciences* a cikin 2013 ya yi jayayya cewa bayanan asali na yawancin waɗannan alamomin sun rasa. Ya yi iƙirarin cewa ciwon daji cuta ce mai matakin nama kuma waɗannan alamomin matakin salon salula suna yaudara.

## Manazarta