33. Tumor cells were isolated from a breast cancer patient. These cells were injected into nude mice and they were divided into four groups. Group 1 received EGF receptor-conjugated with methotrexate; Group 2  received transferrin receptor-conjugated with methotrexate. Group 3 received mannose receptor- conjugated with methotrexate; Group 4 received same amount of the free drug. In which of the following cases tumorigenic index would be minimum?
(1) Free drug
(2) EGF receptor-conjugated drug
(3) Transferrin receptor-conjugated drug
(4) Mannose receptor-conjugated drug

The tumorigenic index would be minimum in the case of:

(2) EGF receptor-conjugated methotrexate

Explanation:

• Breast cancer cells often overexpress the Epidermal Growth Factor Receptor (EGFR), making EGFR a prime target for directed drug delivery.​

• Conjugating methotrexate (MTX) with the EGFR ligand allows targeted delivery to cancer cells, increasing drug uptake by the tumor while sparing normal cells, resulting in increased efficacy and reduced side effects.

• Studies show that receptor-targeted drug delivery systems (like EGFR-conjugated MTX) demonstrate improved cytotoxicity in breast cancer models compared to free drug or non-targeted receptor conjugates.​

• Transferrin receptor and mannose receptor targeting can also enhance drug delivery, but EGFR targeting is particularly effective in breast cancer due to specific receptor overexpression.

• Free methotrexate typically has the least tumor specificity and therefore the highest tumorigenic index.