RB1 biallelic loss, together with TP53 loss, is the molecular hallmark of SCLC (~95% of c...
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | BMA-RB1-SCLC |
|---|---|
| Тип | Клінічна застосовність |
| Статус | переглянуто 2026-05-04 | очікує клінічного підпису | потрібне рев’ю клінічної застосовності |
| Хвороби | DIS-SCLC |
| Джерела | SRC-CASPIAN-PAZ-ARES-2019 SRC-NCCN-SCLC-2025 |
Дані про клінічну застосовність
| Біомаркер | BIO-RB1 |
|---|---|
| Варіант | RB1 biallelic loss (universal in SCLC; defines SCLC molecular signature together with TP53 loss; not a treatment-selecting biomarker in SCLC but essential for diagnosis) |
| Хвороба | DIS-SCLC |
| Рівень ESCAT | IIIB |
| Рекомендовані комбінації | etoposide 100 mg/m² IV days 1–3 + cisplatin 25 mg/m² IV days 1–3 + atezolizumab 1200 mg IV day 1 q21d × 4 cycles, then atezolizumab maintenance (IMpower133 regimen; FDA 2019), etoposide + carboplatin + durvalumab (CASPIAN regimen; FDA 2020) |
| Протипоказана монотерапія | CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) — universally inactive in SCLC due to RB1/pRb loss; pRb is the substrate for CDK4/6 and without it CDK4/6 inhibition has no antiproliferative effect |
| Підсумок доказів | RB1 biallelic loss, together with TP53 loss, is the molecular hallmark of SCLC (~95% of cases have both). RB1 loss is not used to select therapy in SCLC (all SCLC patients receive the same backbone: EP/EC ± atezolizumab/durvalumab); rather, it is a diagnostic characteristic and potential therapeutic vulnerability. RB1 loss renders cells dependent on alternative cell cycle regulators (CDK4/6-independent E2F activation) — this is why CDK4/6 inhibitors have no activity in SCLC (pRb loss negates CDK4/6 inhibition). Investigational targeting of RB1-deficient SCLC: aurora kinase A inhibitors (alisertib — phase II, limited activity); EZH2 inhibitors (tazemetostat — RB1-null tumors may have heightened EZH2 dependence); LSD1 inhibitors; ATR/CHK1 inhibitors (replication stress in RB1-null context). ESCAT IIIB: RB1 loss is diagnostically informative and a conceptual therapeutic target, but no FDA-approved targeted therapy exploiting RB1 deficiency as of 2026. |
Нотатки
ESCAT IIIB: RB1 loss in SCLC is a diagnostic feature and resistance marker (CDK4/6i) but does not select active targeted therapy. Rb protein loss by IHC is used clinically to distinguish SCLC from other high-grade neuroendocrine neoplasms: Rb-negative (SCLC) vs Rb-retained (carcinoid tumors, LCNEC can be variable). SCLC molecular subtypes (ASCL1-high, NEUROD1-high, POU2F3-high, YAP1-high) are emerging as predictors of DLL3 (rovalpituzumab tesirine/tarlatamab) and LSD1 inhibitor response but are separate biomarkers from RB1. Tarlatamab (DLL3-targeted BiTE; FDA 2024 for 2L+ SCLC) does not select based on RB1 status.
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